Methods and Systems for Treating Cardiovascular Disease Using an Implantable Electroacupuncture Device

ABSTRACT

An exemplary method treating a cardiovascular disease in a patient includes 1) generating, by an electroacupuncture device implanted beneath a skin surface of the patient at an acupoint corresponding to a median nerve of the patient, stimulation sessions at a duty cycle that is less than 0.05, wherein the duty cycle is a ratio of T3 to T4, each stimulation session included in the stimulation sessions has a duration of T3 minutes and occurs at a rate of once every T4 minutes, and the electroacupuncture device comprises a central electrode of a first polarity and an annular electrode of a second polarity and that is spaced apart from the central electrode; and 2) applying, by the electroacupuncture device, the stimulation sessions to the median nerve by way of the central electrode and the annular electrode in accordance with the duty cycle.

RELATED APPLICATIONS

The present application is a continuation application of U.S. patentapplication Ser. No. 14/669,155, filed Mar. 26, 2015, which applicationis a divisional application of U.S. patent application Ser. No.13/622,653, filed Sep. 19, 2012 and issued as U.S. Pat. No. 8,996,125.U.S. patent application Ser. No. 13/622,653 also claims priority under35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 61/626,339,filed Sep. 23, 2011; U.S. Provisional Patent Application No. 61/606,995,filed Mar. 6, 2012; U.S. Provisional Patent Application No. 61/609,875,filed Mar. 12, 2012; U.S. Provisional Patent Application No. 61/672,257,filed Jul. 16, 2012; U.S. Provisional Patent Application No. 61/672,661,filed Jul. 17, 2012; U.S. Provisional Patent Application No. 61/673,254,filed Jul. 19, 2012; U.S. Provisional Patent Application No. 61/674,691,filed Jul. 23, 2012; and U.S. Provisional Patent Application No.61/676,275, filed Jul. 26, 2012. All of these applications areincorporated herein by reference in their respective entireties.

BACKGROUND INFORMATION

Cardiovascular disease, also sometimes referred to as heart disease,cardiac disease or cardiopathy, is an umbrella term for a variety ofdiseases affecting the heart. Cardiovascular disease includes any of anumber of specific diseases that affect the heart itself and/or theblood vessel system, especially the veins and arteries leading to andfrom the heart. Cardiovascular disease represents one of the moreprevalent diseases affecting middle-aged and older-aged individuals inboth Western and Eastern societies. As of 2007, cardiovascular diseasewas the leading cause of death in the United States, England, Canada andWales, accounting for 25.4% of the total deaths in the United States.

In the United States, the most common type of cardiovascular disease iscoronary artery disease (CAD). Coronary artery disease is a disease ofthe artery caused by the accumulation of atheromatous plaques within thewalls of the arteries that supply the myocardium (the heart muscle).Angina pectoris (chest pain) and myocardial infarction (heart attack)are symptoms of and conditions caused by coronary artery disease.

Another type of cardiovascular disease is ischemic heart disease.Ischemia is defined as the inadequate flow of blood to a part of thebody caused by constriction or blockage of the blood vessels supplyingit. Ischemia of the heart muscle produces angina pectoris. Anginapectoris may be classified as either stable angina pectoris or unstableangina pectoris. Stable angina pectoris is angina pectoris induced byexercise and relieved by rest. Stable angina pectoris occurs when thedemand for blood by the heart exceeds the supply of the blood providedby the coronary arteries.

Unstable angina pectoris, also known as “crescendo angina,” is a form ofacute coronary syndrome. It is defined as angina pectoris that changesor worsens. It occurs unpredictably at rest and may be a seriousindicator of an impending heart attack. What differentiates stableangina from unstable angina (other than symptoms) is the pathophysiologyof the atherosclerosis. The pathophysiology of unstable angina is thereduction of coronary flow due to transient platelet aggregation. Instable angina, the developing atheroma is protected with a fibrous cap.This cap (atherosclerotic plaque) may rupture in unstable angina,allowing blood clots to precipitate and further decrease the lumen ofthe coronary vessel. This explains why an unstable angina appears to beindependent of activity.

There are currently a wide variety of methods that can be used to treatpatients with cardiovascular diseases. These include risk factorreduction (e.g., diet, exercise, stress reduction), pharmacologictherapy (drugs), and invasive and interventional therapies as practicedby cardiologists and surgeons (e.g., bypass surgery).

Despite all the therapeutic measures available and practiced today, manypatients remain severely incapacitated by their cardiovascular disease.Thus, in recent years there has been both a profound interest andacceptance of a number of alternative therapies. These therapies haveemerged because none of the more usual therapies have been completelyeffective in eliminating either the symptoms or the adverse outcomesresulting from these diseases. Further, many mainstay therapies areassociated with side effects that surprising numbers of patients findunacceptable. Therefore, there has been a surge of interest inalternative therapies. See, e.g., J. C. Longhurst “Central andPeripheral Neural Mechanisms of Acupuncture in Myocardial Ischemia”,International Congress Series 1238 (2002) 79-87 (hereafter “Longhurst(2002)”); C. Mannheimer et al., “The Problem of Chronic RefractoryAngina,” European Heart Journal (2002) 23, 355-370 (hereafter“Mannheimer (2002)”); J. E. Sanderson, “Electrical Neurostimulators forPain Relief in Angina,” British Heart Journal (1990) 63:141-143(hereafter “Sanderson (1990)”).

The alternative approaches that have emerged in the medical managementof cardiovascular disease include neuromodulation techniques; e.g.,transcutaneous electric nerve stimulation (TENS) and spinal cordstimulation (SCS). Mannheimer (2002) at 360-362.

Neuromodulation techniques, including both TENS and SCS, appear to besafe and generally effective methods of treating angina pectoris.Transcutaneous electric nerve stimulation (TENS) is a neuromodulationtechnique that is comparable to needle acupuncture. However, instead ofneedles, standard electrodes are applied over the painful area of thechest wall. The device can usually be used by the patient at home afterinstruction. When an angina attack occurs or is anticipated, the patientapplies stimulation for one to three minutes. It is essential to placethe electrodes so that the stimulation paresthesia cover the area ofangina pain, as this is the only way to ensure that the proper spinalsegment is activated; i.e., the segment that supplies the heart withnerves. Id at 361.

Disadvantageously, skin irritation develops in a large number ofpatients, making it difficult to continue with this form of TENStherapy. Thus, if long term neuromodulation treatment is needed, as inangina, spinal cord stimulation (SCS) is typically used as a preferabletreatment modality. Clinical observations also suggest that spinal cordstimulation may be more effective than TENS. Thus, TENS has recentlybeen used more as a test method for planned implantation, to determinewhether myocardial ischemia is really the cause of the patient's painand to evaluate whether the patient shows good enough compliance tohandle a spinal cord stimulator. Id.

Spinal cord stimulation requires implantation surgery. Implantation ofthe spinal cord system is performed under local anesthesia. Theelectrode is positioned epidurally so that paresthesia is produced inthe region of angina pain radiation. The patient carries an implantablepulse generator in a subcutaneous pouch, typically below the left costalarch (rib cage). The electrode is then connected to the pulse generatorby tunneling a subcutaneous lead from the epidural space (adjacent thespine on the back side of the patient) to the subcutaneous pouch belowthe patient's rib cage (on the front side of the patient). The system issimilar to a pacemaker with the electrode placed in the epidural spaceinstead of the heart. Id.

The TENS and SCS methods described above are potent and are capable of,at least temporarily (in the case of TENS), treating myocardialischemia, such as angina pectoris. However, the use of TENS providesonly temporary relief, and use of an SCS system is highly invasive andhas potentially debilitating side effects. To use an SCS device to treatangina pectoris requires that a lead must be tunneled all the way fromthe back side of the patient to the front side of the patient. Such amethod is as invasive as, and suffers from most of the same problems as,any major surgery. In addition, the complications associated withtunneling and removal of leads, which include infection, breakage, aswell as the need to perform additional surgery, are not trivial.

Another alternative approach for treating cardiovascular disease, and ahost of other physiological conditions, illnesses and deficiencies, isacupuncture, which includes traditional acupuncture, acupressure.Acupuncture has been practiced in Eastern civilizations (principallyChina, but also other Asian countries) for at least 2500 years. It isstill practiced today throughout many parts of the world, including theUnited States and Europe. A good summary of the history of acupuncture,and its potential applications may be found in Cheung, et al., “TheMechanism of Acupuncture Therapy and Clinical Case Studies”, (Taylor &Francis, publisher) (2001) ISBN 0-415-27254-8, hereafter referred to as“Cheung, Mechanism of Acupuncture, 2001.” The Forward, as well asChapters 1-3, 5, 7, 8, 12 and 13 of Cheung, Mechanism of Acupuncture,2001, are incorporated herein by reference.

Despite the practice in Eastern countries for over 2500 years, it wasnot until President Richard Nixon visited China (in 1972) thatacupuncture began to be accepted in Western countries, such as theUnited States and Europe. One of the reporters who accompanied Nixonduring his visit to China, James Reston, from the New York Times,received acupuncture in China for post-operative pain after undergoingan emergency appendectomy under standard anesthesia. Reston experiencedpain relief from the acupuncture and wrote about it in The New YorkTimes. In 1973 the American Internal Revenue Service allowed acupunctureto be deducted as a medical expense. Following Nixon's visit to China,and as immigrants began flowing from China to Western countries, thedemand for acupuncture increased steadily. Today, acupuncture therapy isviewed by many as a viable alternative form of medical treatment,alongside Western therapies. Moreover, acupuncture treatment is nowcovered, at least in part, by most insurance carriers. Further, paymentfor acupuncture services consumes a not insignificant portion ofhealthcare expenditures in the U.S. and Europe. See, generally, Cheung,Mechanism of Acupuncture, 2001, vii.

Acupuncture is an alternative medicine that treats patients by insertionand manipulation of needles in the body at selected points. Novak,Patricia D. et al (1995). Dorland's Pocket Medical Dictionary (25thed.), Philadelphia: (W.B. Saunders Publisher), ISBN 0-7216-5738-9. Thelocations where the acupuncture needles are inserted are referred toherein as “acupuncture points” or simply just “acupoints”. The locationof acupoints in the human body has been developed over thousands ofyears of acupuncture practice, and maps showing the location ofacupoints in the human body are readily available in acupuncture booksor online. Acupoints are typically identified by various letter/numbercombinations, e.g., L6, S37. The maps that show the location of theacupoints may also identify what condition, illness or deficiency theparticular acupoint affects when manipulation of needles inserted at theacupoint is undertaken.

References to the acupoints in the literature are not always consistentwith respect to the format of the letter/number combination. Someacupoints are identified by a name only, e.g., Tongi. The same acupointmay be identified by others by the name followed with a letter/numbercombination placed in parenthesis, e.g., Tongi (HT5). Alternatively, theacupoint may be identified by its letter/number combination followed byits name, e.g., HT5 (Tongi). The first letter typically refers to a bodyorgan, or other tissue location associated with, or affected by, thatacupoint. However, usually only the letter is used in referring to theacupoint, but not always. Thus, for example, the acupoint P-6 is thesame as acupoint Pericardium 6 which is the same as PC-6 which is thesame as Pe 6 which is the same as Neiguan. For purposes of this patentapplication, unless specifically stated otherwise, all references toacupoints that use the same name, or the same first letter and the samenumber, and regardless of slight differences in second letters andformatting, are intended to refer to the same acupoint. Thus, forexample, the acupoint Neiguan is the same acupoint as Neiguan (P6),which is the same acupoint as Neiguan (PC6), which is the same acupointas PC6 (Neiguan), which is the same acupoint as Neiguan (PC-6), which isthe same acupoint as Neiguan (Pe-6), which is the same acupoint as P6, P6, PC6 or PC-6 or Pe 6.

An excellent reference book that identifies all of the traditionalacupoints within the human body is WHO STANDARD ACUPUNCTURE POINTLOCATIONS IN THE WESTERN PACIFIC REGION, published by the World HealthOrganization (WHO), Western Pacific Region, 2008 (updated and reprinted2009), ISBN 978 92 9061 248 7 (hereafter “WHO Standard Acupuncture PointLocations 2008”). The Table of Contents, Forward (page v-vi) and GeneralGuidelines for Acupuncture Point Locations (pages 1-21), as well aspages 151 and 154 (which pages illustrate with particularity thelocation of acupoint PC6) of the WHO Standard Acupuncture PointLocations 2008 are referred to herein as Appendix D.

While many in the scientific and medical community are highly criticalof the historical roots upon which acupuncture has developed, (e.g.,claiming that the existence of meridians, qi, yin and yang, and the likehave no scientific basis), see, e.g.,http://en.wikipedia.org/wiki/Acupuncture, few can refute the vast amountof successful clinical and other data, accumulated over centuries ofacupuncture practice, that shows needle manipulation applied at certainacupoints is quite effective.

The World Health Organization and the United States' National Institutesof Health (NIH) have stated that acupuncture can be effective in thetreatment of neurological conditions and pain. Reports from the USA'sNational Center for Complementary and Alternative Medicine (NCCAM), theAmerican Medical Association (AMA) and various USA government reportshave studied and commented on the efficacy of acupuncture. There isgeneral agreement that acupuncture is safe when administered bywell-trained practitioners using sterile needles, but not on itsefficacy as a medical procedure.

An early critic of acupuncture, Felix Mann, who was the author of thefirst comprehensive English language acupuncture textbook Acupuncture:The Ancient Chinese Art of Healing, stated that “The traditionalacupuncture points are no more real than the black spots a drunkard seesin front of his eyes.” Mann compared the meridians to the meridians oflongitude used in geography—an imaginary human construct. Mann, Felix(2000). Reinventing acupuncture: a new concept of ancient medicine.Oxford: Butterworth-Heinemann. pp. 14; 31. ISBN 0-7506-4857-0. Mannattempted to combine his medical knowledge with that of Chinese theory.In spite of his protestations about the theory, however, he apparentlybelieved there must be something to it, because he was fascinated by itand trained many people in the West with the parts of it he borrowed. Healso wrote many books on this subject. His legacy is that there is now acollege in London and a system of needling that is known as “MedicalAcupuncture”. Today this college trains doctors and Western medicalprofessionals only.

For purposes of this patent application, the arguments for and againstacupuncture are interesting, but not that relevant. What is important isthat a body of literature exists that identifies several acupointswithin the human body that, rightly or wrongly, have been identified ashaving an influence on, or are otherwise somehow related to, thetreatment of various physiological conditions, deficiencies orillnesses, including pain and other conditions associated withmyocardial ischemia, such as angina pectoris. With respect to theseacupoints, the facts speak for themselves. Either these points do or donot affect the conditions, deficiencies or illnesses with which theyhave been linked. The problem lies in trying to ascertain what is factfrom what is fiction. This problem is made more difficult whenconducting research on this topic because the insertion of needles, andthe manipulation of the needles once inserted, is more of an art than ascience, and results from such research become highly subjective. Whatis needed is a much more regimented approach for doing acupunctureresearch.

It should also be noted that other medical research, not associated withacupuncture research, has over the years identified nerves and otherlocations throughout a patient's body where the application ofelectrical stimulation produces a beneficial effect for the patient.Indeed, the entire field of neurostimulation deals with identifyinglocations in the body where electrical stimulation can be applied inorder to provide a therapeutic effect for a patient. For purposes ofthis patent application, such known locations within the body aretreated essentially the same as acupoints—they provide a “target”location where electrical stimulation may be applied to achieve abeneficial result, whether that beneficial result is to reduce pain, totreat myocardial ischemia, to treat hypertension, to mitigate some otherform of cardiovascular disease or to address some other issue associatedwith a disease or condition of the patient.

Returning to the discussion regarding acupuncture, some have proposedapplying moderate electrical stimulation at selected acupuncture pointsthrough needles that have been inserted at those points. Such electricalstimulation is known as electroacupuncture (EA). According toAcupuncture Today, a trade journal for acupuncturists:“Electroacupuncture is quite similar to traditional acupuncture in thatthe same points are stimulated during treatment. As with traditionalacupuncture, needles are inserted on specific points along the body. Theneedles are then attached to a device that generates continuous electricpulses using small clips. These devices are used to adjust the frequencyand intensity of the impulse being delivered, depending on the conditionbeing treated. Electroacupuncture uses two needles at a time so that theimpulses can pass from one needle to the other. Several pairs of needlescan be stimulated simultaneously, usually for no more than 30 minutes ata time.” “Acupuncture Today: Electroacupuncture”. 2004 2 Jan.

Recent research has reported the use of electroacupuncture (EA) for thetreatment of myocardial ischemia and pain relief in angina. See, e.g.,J. Gao, et al., “Acupuncture pretreatment protects heart from injury inrats with myocardial ischemia and reperfusion via inhibition of the₁-adrenoceptor signaling pathway,” Life Sciences 80 (2007) 1484-1489(hereafter “Gao (2007)”); Longhurst (2002); P. Li et al., “Reversal ofReflex-Induced Myocardial Ischemia by Median Nerve Stimulation: A FelineModel of Electroacupuncture,” American Heart Association Circulation1998, 97:1186-1194 (hereafter “Li (1998)”); Sanderson (1990).

The reason why acupuncture, including EA, can be used to treat angina isdiscussed at length in Cheung, Mechanism of Acupuncture, 2001, chapter8, previously incorporated herein by reference.

Similar techniques for using electrical devices, including external EAdevices, for stimulating peripheral nerves and other body locations fortreatment of various maladies are known in the art. See, e.g., U.S. Pat.Nos. 4,535,784; 4,566,064; 5,195,517; 5,250,068; 5,251,637; 5,891,181;6,393,324; 6,006,134; 7,171,266; and 7,171,266. The methods and devicesdisclosed in these patents, however, typically utilize either largeimplantable stimulators having long leads that must be tunneled throughtissue to reach the desired stimulation site, or use external devicesthat must interface with implanted electrodes via percutaneous leads orwires passing through the skin. Such devices and methods are still fartoo invasive, or are ineffective, and thus are subject to the samelimitations and concerns, as are the previously described electricalstimulation devices.

From the above, it is seen that there is a need in the art for a lessinvasive device and technique for electroacupuncture stimulation ofacupoints that does not require the continual use of needles insertedthrough the skin, or long insulated wires implanted or inserted intoblood vessels, for the purposes of treating cardiovascular diseases.

SUMMARY

One characterization of the invention described herein is an ImplantableElectroAcupuncture System (IEAS) that treats cardiovascular diseasethrough application of electroacupuncture (EA) stimulation pulsesapplied at a specified tissue location(s) of a patient. A key componentof such IEAS is an implantable electroacupuncture (EA) device. The EAdevice has a small, hermetically-sealed housing containing a primarypower source, pulse generation circuitry powered by the primary powersource, and a sensor that wirelessly senses operating commands generatedexternal to the housing. The pulse generation circuitry generatesstimulation pulses in accordance with a specified stimulation regimen ascontrolled, at least in part, by the operating commands sensed throughthe sensor. The EA device further includes a plurality of electrodearrays (where an electrode array comprises an array of n conductivecontacts electrically joined together to function jointly as oneelectrode, where n is an integer less than 300) on the outside of the EAdevice housing that are electrically coupled to the pulse generationcircuitry on the inside of the EA device housing. Such electricalcoupling occurs through at least one feed-through terminal passingthrough a wall of the hermetically-sealed housing. Stimulation pulsesgenerated by the pulse generation circuitry inside of the EA devicehousing are directed to the electrode arrays on the outside of the EAhousing. The stimulation pulses are thus applied at the specified tissuelocation through the plurality of electrode arrays in accordance withthe specified stimulation regimen. The specified stimulation regimendefines how often a stimulation session (a stimulation session comprisesa stream of stimulation pulses) is applied to the patient, and theduration of each stimulation session. Moreover, the stimulation regimenrequires that the stimulation session be applied at a very low dutycycle. More particularly, if the stimulation session has a duration ofT3 minutes and occurs at a rate of once every T4 minutes, then the dutycycle, or the ratio of T3/T4, cannot be greater than 0.05.

Another characterization of the invention described herein is anImplantable ElectroAcupuncture System (IEAS) for treating heart failure,coronary artery disease, myocardial ischemia or angina of a patient.Such IEAS includes (a) an implantable electroacupuncture (EA) devicehousing having a maximum linear dimension of no more than 25 mm in afirst plane, and a maximum height of no more 2.5 mm in a second planeorthogonal to the first plane; (b) a primary battery within the EAdevice housing having an internal impedance of no less than about 5ohms; (c) pulse generation circuitry within the EA device housing andpowered by the primary battery that generates stimulation pulses duringa stimulation session; (d) control circuitry within the EA devicehousing and powered by the primary battery that controls the frequencyof the stimulation sessions to occur no more than once every T4 minutes,and that further controls the duration of each stimulation session tolast no longer than T3 minutes, where the ratio of T3/T4 is no greaterthan 0.05; (e) sensor circuitry within the EA device housing and coupledto the control circuitry that is responsive to the presence of a controlcommand generated external to the EA device housing, which controlcommand when received by the control circuitry sets the times T3 and T4to appropriate values; and (f) a plurality of electrodes located outsideof the EA device housing that are electrically coupled to the pulsegeneration circuitry within the EA device housing.

Use of the IEAS described herein advantageously allows stimulationpulses of the stimulation sessions to be applied to body tissue of thepatient located in the vicinity of the plurality of electrodes. Bystrategically positioning the plurality of electrodes near at least oneselected acupoint of the patient known to moderate or positively affectheart failure, coronary artery disease, myocardial ischemia or angina ofthe patient, such condition can be effectively treated over time.

A preferred acupoint to use with the IEAS for the purposes describedherein is at least one of the following acupoints: PC6 in the right orleft forearm; ST36 on the anterior aspect of the left or right leg, onthe tibialis anterior muscle; BL14 (also referred to as UB14), in theupper back region; EX-HN1 (located approximately one centimeter fromGV20, on the top of the head); HT7 on the anteromedial aspect of theright or left wrist, radial to the flexor carpi ulnaris tendon, on thepalmar wrist crease; HT5 on the anteromedial aspect of the forearm,radial to the flexor carpi ulnaris tendon; LI11 on the lateral aspect ofthe elbow; LU2 on the anterior thoracic region, in the depression of theinfraclavicular fossa; and LU7 on the radial aspect of the forearm,between the tendons of the abductor pollicis longus and the extensorpollicis brevis muscles.

Yet another characterization of the invention described herein is amethod for treating cardiovascular disease in a patient. The methodincludes: (a) implanting an electroacupuncture (EA) device in thepatient below the patient's skin at or near at least one specifiedacupoint; (b) enabling the EA device to generate stimulation sessions ata duty cycle that is less than 0.05, wherein each stimulation sessioncomprises a series of stimulation pulses, and wherein the duty cycle isthe ratio of T3/T4, where T3 is the duration of each stimulationsession, and T4 is the time or duration between stimulation sessions;and (c) delivering the stimulation pulses of each stimulation session tothe specified acupoint through a plurality of electrode arrayselectrically connected to the EA device. Here, an electrode arraycomprises an array of n conductive contacts electrically joined togetherto function jointly as one electrode, where n is an integer from 1 to30. The specified acupoint to use for this method is preferably one ofthe nine acupoints identified above in the previous paragraph.

A further characterization of the invention described herein is a methodof treating heart failure, coronary artery disease, myocardial ischemiaor angina in a patient using a small implantable electroacupuncturedevice (IEAD). Such IEAD is powered by a small disc primary batteryhaving a specified nominal output voltage of about 3 volts and having aninternal impedance of at least 5 ohms. The IEAD is configured, usingelectronic circuitry within the IEAD, to generate stimulation pulses inaccordance with a specified stimulation regimen. These stimulationpulses are applied at a selected tissue location of the patient throughat least two electrodes located outside of the housing of the IEAD. Themethod comprises: (a) implanting the IEAD below the skin surface of thepatient at or near at least one acupoint selected from the group ofacupoints that includes: PC6, ST36, BL14 (also referred to as UB14),EX-HN1 (located approximately one centimeter from GV20), HT7, HT5, LI11,LU2 and LU7; and (b) enabling the IEAD to provide stimulation pulses inaccordance with a stimulation regimen that provides a stimulationsession of duration T3 minutes at a rate of once every T4 minutes, wherethe ratio of T3/T4 is no greater than 0.05, and wherein T3 is at least10 minutes and no greater than 60 minutes.

The invention described herein may additionally be characterized as amethod of assembling an implantable electroacupuncture device (IEAS) ina small, thin, hermetically-sealed, housing having a maximum lineardimension in a first plane of no more than 25 mm and a maximum lineardimension in a second plane orthogonal to the first plane of no morethan 2.5 mm. Such housing has at least one feed-through pin assemblyradially passing through a wall of the thin housing that isolates thefeed-through pin assembly from high temperatures and residual weldstresses that occur when the thin housing is welded shut tohermetically-seal its contents. The method comprises the steps of:

-   -   (a) forming a thin housing having a bottom case and a top cover        plate, the top cover plate being adapted to fit over the bottom        case, the bottom case having a maximum linear dimension of no        more than 25 mm;    -   (b) forming a recess in a wall of the housing;    -   (c) placing a feed-through assembly within the recess so that a        feed-through pin of the feed-through assembly electrically        passes through a wall of the recess at a location that is        separated from where the wall of the housing is designed to        contact the top cover plate; and    -   (d) welding the top cover plate to the bottom case around a        perimeter of the bottom case, thereby hermetically sealing the        bottom case and top case together.

Yet another characterization of the invention described herein is anImplantable ElectroAcupuncture System (IEAS) for treating heart failure,coronary artery disease, myocardial ischemia or angina. Such IEASincludes (a) at least one external component, and (b) a small, thinimplantable component having a maximum linear dimension in a first planeof less than 25 mm, and a maximum linear dimension in a second planeorthogonal to the first plan of no more than 2.5 mm.

In one preferred embodiment, the external component comprises anelectromagnetic field generator. As used herein, the term“electromagnetic field” encompasses radio frequency fields, magneticfields, light emissions, or combinations thereof.

The implantable component includes a housing made of a bottom part and atop part that are welded together to create an hermetically-sealed,closed container. At least one feed-through terminal passes through aportion of a wall of the top part or bottom part. This terminal allowselectrical connection to be made between the inside of the closedcontainer and a location on the outside of the closed container.Electronic circuitry, including a power source, is included on theinside of the closed container that, when enabled, generates stimulationpulses during a stimulation session that has a duration of T3 minutes.The electronic circuitry also generates a new stimulation session at arate of once every T4 minutes. The ratio of T3/T4, or the duty cycle ofthe stimulation sessions, is maintained at a very low value of nogreater than 0.05. The stimulation pulses are coupled to the at leastone feed-through terminal, where they are connected to a plurality ofelectrodes/arrays located on an outside surface of the closed housing.The stimulation pulses contained in the stimulation sessions are thusmade available to stimulate body tissue in contact with or near theplurality of electrodes/arrays on the outside of the closed housing.

Further included on the inside of the closed container is a sensoradapted to sense the presence or absence of an electromagnetic field.Also included on the inside of the closed container is a power sourcethat provides operating power for the electronic circuitry.

In operation, the external component modulates an electromagnetic fieldwhich, when sensed by the sensor inside of the closed container, conveysinformation to the electronic circuitry inside of the closed housingthat controls when and how long the stimulation sessions are appliedthrough the plurality of electrodes/arrays. Once this information isreceived by the electronic circuitry, the external component can beremoved and the implantable component of the IEAS will carry out thestimulation regimen until the power source is depleted or newinformation is received by the electronic circuitry, whichever occursfirst.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other aspects, features and advantages of the inventionwill be more apparent from the following more particular descriptionthereof, presented in conjunction with the following drawings. Thesedrawings illustrate various embodiments of the principles describedherein and are part of the specification. The illustrated embodimentsare merely examples and do not limit the scope of the disclosure.

FIGS. 1-16 relate to one preferred embodiment of the invention. FIGS.17-31 relate to general principles and concepts associated with theinvention.

FIG. 1 is a perspective view of an Implantable Electroacupuncture Device(IEAD) made in accordance with the teachings presented herein.

FIG. 1A shows a view of a patient's limb (arm or leg) where an acupointhas been identified, and illustrates the manner used to implant an IEADat the selected acupoint.

FIG. 1B shows a sectional view of an IEAD implanted at a selectedacupoint, and illustrates the electric field gradient lines created whenan electroacupuncture (EA) pulse is applied to the tissue through thecentral electrode and ring electrode attached to the bottom surface andperimeter edge, respectively, of the IEAD housing.

FIG. 2 shows a plan view of the bottom surface of the IEAD housingillustrated in FIG. 1.

FIG. 2A shows a side view of the IEAD housing illustrated in FIG. 1.

FIG. 3 shows a plan view of one side, indicated as the “skin” side, ofthe IEAD housing or case illustrated in FIG. 1.

FIG. 3A is a sectional view of the IEAD of FIG. 3 taken along the lineA-A of FIG. 3.

FIG. 4 is a perspective view of the IEAD housing, including afeed-through pin, before the electronic components are placed therein,and before being sealed with a “skin side” cover plate.

FIG. 4A is a side view of the IEAD housing of FIG. 4.

FIG. 5 is a plan view of the empty IEAD housing shown in FIG. 4.

FIG. 5A depicts a sectional view of the IEAD housing of FIG. 5 takenalong the section line A-A of FIG. 5.

FIG. 5B shows an enlarged view or detail of the portion of FIG. 5A thatis encircled with the line B.

FIG. 6 is a perspective view of an electronic assembly, including abattery, that is adapted to fit inside of the empty housing of FIG. 4and FIG. 5.

FIGS. 6A and 6B show a plan view and side view, respectively, of theelectronic assembly shown in FIG. 6.

FIG. 7 is an exploded view of the IEAD assembly, illustrating itsconstituent parts.

FIG. 7A schematically illustrates a few alternative electrodeconfigurations that may be used with the invention.

FIG. 8A illustrates a functional block diagram of the electroniccircuits used within an IEAD of the type described herein.

FIG. 8B shows a basic boost converter circuit configuration, and is usedto model how the impedance of the battery RBAT can affect itsperformance.

FIG. 9A illustrates a typical voltage and current waveform for thecircuit of FIG. 8 when the battery impedance RBAT is small.

FIG. 9B shows the voltage and current waveform for the circuit of FIG.8B when the battery impedance RBAT is large.

FIG. 10 shows one preferred boost converter circuit and a functionalpulse generation circuit configuration for use within the IEAD.

FIG. 11 shows an alternate boost converter circuit configuration and afunctional pulse generation circuit for use within the IEAD.

FIG. 12 shows a refinement of the circuit configuration of FIG. 11.

FIG. 13A shows one preferred schematic configuration for an implantableelectroacupuncture device (IEAD) that utilizes the boost converterconfiguration shown in FIG. 10.

FIG. 13B shows current and voltage waveforms associated with theoperation of the circuit shown in FIG. 13A.

FIG. 14 shows another preferred schematic configuration for an IEADsimilar to that shown in FIG. 13A, but which uses an alternate outputcircuitry configuration for generating the stimulus pulses.

FIG. 15A shows a timing waveform diagram of representative EAstimulation pulses generated by the IEAD device during a stimulationsession.

FIG. 15B shows a timing waveform diagram of multiple stimulationsessions, and illustrates the waveforms on a more condensed time scale.

FIG. 16 shows a state diagram that shows the various states in which theIEAD may be placed through the use of an external magnet.

FIG. 17 is a block diagram that illustrates the two main components ofan Electroacupuncture (EA) Stimulation System made as taught herein.Such EA Stimulation System (also referred to herein as an “EA System”)includes: (1) an External Control Device (ECD); and (2) an ImplantableStimulator (also referred to herein as an “ImplantableElectroacupuncture Device” or IEAD). Two variations of the IEAD aredepicted, either one of which could be used as part of the EA System,one having electrodes formed as an integral part of the IEAD housing,and another having the electrodes at or near the distal end of a veryshort lead that is attached to the IEAD.

FIG. 18 is a Table that summarizes the functions performed by the twomain components of the EA System of FIG. 1A in accordance with variousconfigurations of the invention.

FIG. 19 is an illustration of the human body, and shows the location ofsome effective and ineffective acupoints used in electroacupuncture forthe treatment of cardiovascular disease, hypertension and othermaladies. This figure is taken from Li et al., “Neural Mechanism ofElectroacupuncture's Hypotensive Effects”, Autonomic Neuroscience: Basicand Clinical 157 (2010) 24-30. A much more detailed representation ofthese and other acupoints may be found in WHO Standard Acupuncture PointLocations 2008, selected portions of which may be found in Appendix D.

FIG. 20 shows the use of one type of electrode integrated within theunderneath side (the side farthest away from the skin) of a housingstructure of an implantable electroacupuncture device, or IEAD. Thiselectrode is insulated from the other portions of the IEAD housing,which other portions of the housing structure may function as a returnelectrode for electroacupuncture stimulation.

FIG. 20A is a sectional view, taken along the line A-A of FIG. 20, thatshows one embodiment or variation of the IEAD housing wherein theelectrode of FIG. 20 resides in a cavity formed within the underneathside of the IEAD.

FIG. 20B is a sectional view, taken along the line A-A of FIG. 20, andshows an alternative embodiment or variation of the underneath side ofthe IEAD housing wherein the electrode comprises a smooth bump thatprotrudes out from the underneath surface of the IEAD a short distance.

FIG. 20C is a sectional view, taken along the line A-A of FIG. 20, andshows yet an additional alternative embodiment or variation of theunderneath side of the IEAD housing wherein the electrode is at or nearthe distal end of a short lead that extends out a short distance fromthe underneath side of, or an edge of, the IEAD housing.

FIG. 21 is similar to FIG. 20, but shows the use of an electrode arrayhaving four individual electrodes integrated within the housingstructure of an IEAD.

FIG. 21A is a sectional view, taken along the line B-B of FIG. 21, thatshows an embodiment where the electrodes comprise rounded bumps thatprotrude out from the underneath surface of the IEAD a very shortdistance.

FIG. 21B is likewise a sectional view, taken along the line B-B of FIG.21, that shows an alternative embodiment or variation where theelectrodes comprise tapering cones or inverted-pyramid shaped electrodesthat protrude out from the underneath surface of the IEAD a shortdistance and end in a sharp tip, much like a needle.

FIG. 21C is a also a sectional view, taken along the line B-B of FIG.21, that shows yet another embodiment or variation of the underneathsurface of the IEAD housing where the electrodes comprise smallconductive pads formed at or near the distal end of a flex circuit cable(shown twisted 90 degrees in FIG. 21C) that extends out from theunderneath surface of the IEAD housing a short distance.

FIGS. 22A through 22E show various alternate shapes of the housing ofthe IEAD that may be used with an EA System. Each respective figure,FIG. 22A, FIG. 22B, FIG. 22C, and FIG. 22D show side sectional views ofthe housing shape, and FIG. 22E shows both a perspective view (labeledas “A”) and a side view (labeled as “B”) of the housing shape.

FIG. 23 is an electrical functional block diagram of the circuitry andelectrical components housed within an EA System which includes an IEADand External Controller in accordance with the various embodiments ofthe invention. The functional circuitry shown to the right of FIG. 23 iswhat is typically housed within the IEAD. The functional circuitry shownto the left of FIG. 23 is what is typically housed within the ExternalController. How much circuitry is housed within the IEAD and how much ishoused within the External Controller is a function of which embodimentof the EA System is being used.

FIG. 24 is an electrical functional block diagram of a passive IEAD(where “passive”, as used herein, means a circuit that generally employsonly wires or conductors, capacitors, or resistors, and requires nointernal power source). This passive IEAD is intended for use withEmbodiment III (FIG. 18).

FIG. 25A is an electrical functional block diagram of a voltagestimulation output stage that may be used within the IEAD (right side ofFIG. 23).

FIG. 25B is an electrical functional block diagram of a currentstimulation output stage that may be used within the IEAD (right side ofFIG. 23) instead of the voltage stimulation output state of FIG. 25A.

FIG. 26 illustrates one embodiment of a power source that may be usedwithin the IEAD which utilizes both a supercapacitor and a rechargeablebattery.

FIG. 27 is a timing diagram that illustrates a typical stimulationpattern of biphasic stimulation pulses used by the EA System, anddefines some of the operating parameters that may be programmed as partof the programmed stimulation regime.

FIG. 28 is likewise a timing diagram that illustrates, on a larger timescale than FIG. 27, various stimulation patterns and operatingparameters that may be programmed for use by the EA System.

FIG. 29 is a flowchart that illustrates a typical EA stimulation processor method for use with the EA stimulation system described herein.

FIG. 30 is a flowchart that illustrates a manually triggered EAstimulation process or method for use with the EA stimulation systemdescribed herein.

FIG. 31 is an alternate flowchart that illustrates anotherrepresentative EA stimulation process or method that may be used withsome embodiments of the IEAD described herein.

Appendix A illustrates some examples of alternate symmetrical electrodeconfigurations that may be used with an IEAD of the type describedherein.

Appendix B illustrates a few examples of non-symmetrical electrodeconfigurations that may be used with an IEAD made in accordance with theteachings herein.

Appendix C shows an example of the code used in the micro-controller IC(e.g., U2 in FIG. 14) to control the basic operation and programming ofthe IEAD, e.g., to Turn the IEAD ON/OFF, adjust the amplitude of thestimulus pulse, and the like, using only an external magnet as anexternal communication element.

Appendix D contains selected pages from the WHO Standard AcupuncturePoint Locations 2008 reference book, referred to previously, as well asselected pages from other references.

Appendix E shows alternate case shapes and electrode placements for animplantable EA device of the type disclosed herein.

Appendix F illustrates alternate approaches for use with a short pigtaillead attached to the housing of the EA stimulation device.

Appendices A, B, C, D, E and F were submitted one or more of Applicant'sparent applications and are incorporated by reference herein.

Throughout the drawings and appendices, identical reference numbersdesignate similar, but not necessarily identical, elements.

DETAILED DESCRIPTION Overview

Disclosed and claimed herein is a small electroacupuncture (EA) device,having one or more electrodes formed within and as an integral part of,or anchored to, its housing. The EA device is adapted to be implantedthrough a very small incision, e.g., less than 2-3 cm in length,directly adjacent to a selected acupuncture site known to moderate oraffect a patient's physiological or health condition that needstreatment. In accordance with the teachings herein, the small EA deviceis implanted so that its electrodes are located and anchored preciselyat a target acupuncture site. (An acupuncture site may also be referredto herein as an “acupoint.”) When a precise physical location of theelectrode(s) is not achieved through implantation, electrical fieldsemanating from two or more electrodes of the EA device may be combinedor superimposed so as to create a virtual electrode whose virtualposition may be finely adjusted to be precisely at the desired acupoint.

Once the electrode(s) are anchored at the selected acupuncture site,electrical stimulation is applied using a low intensity, low frequencyand low duty cycle stimulation regime that is designed to achieve thesame or similar beneficial therapeutic effects as have previously beenobtained through conventional acupuncture treatments or nervestimulations. One of the primary advantages and benefits provided by theEA device disclosed herein (used to electrically stimulate acupoints) isthat an entire body of medicine (acupuncture, as developed and maturedover thousands of years) may be brought to the general populace with amuch more uniform approach than has heretofore been achievable.

As used herein, note that “EA device” may refer to either a smallImplantable NeuroStimulator (INS) designed for stimulating nerves and/orother body tissue at a precisely-defined location; or a smallimplantable electroacupuncture (EA) device, or “IEAD”, designed tostimulate an acupuncture site, or acupoint, where an “acupoint” isinherently defined as a precise tissue location. Thus, as used herein,IEAD=EA device=implanted neurostimulator=INS. And, as used herein,acupoint=an acupuncture stimulation point=a target tissue/nervestimulation location where electrical pulses generated by aneurostimulator device, i.e., an EA device, are applied.

Also, as used herein, “electrode” and ‘electrode contact” or“electrodes” and “electrode contacts” or electrode array, are often usedinterchangeably to refer to that part of the EA device housing, or thatpart of a lead connected to an EA or INS device, from which electricalstimulation pulses, currents and/or voltages are applied to body tissue.

Applying the EA stimulation according to a prescribed stimulation regimeis an important key of the invention because it allows a more uniformhealth care approach to be followed for treatment of a particulardisorder or illness. Conventional acupuncture treatment, on the otherhand, relies heavily on the skill and experience of the acupuncturist,which may vary a great deal from acupuncturist to acupuncturist. Incontrast, electroacupuncture treatment as taught herein may be uniformlyapplied for a specific disorder or illness once the electrodes arepositioned at or near the correct acupoint, or other tissue locationknown to affect a condition being treated, and once the prescribedstimulation regime is shown to be effective.

Applying the EA stimulation at low intensities, low frequencies and lowduty cycles is also a key feature of the invention because it allows thepower source of the EA device to be small, yet still with sufficientcapacity to uniformly carry out the stimulation procedure (orstimulation regime) for several years, thereby reducing the amount oftime a patient has to spend at the office of medical personnel who aremonitoring or otherwise overseeing the patient's treatment.

Further, having the EA device be small, with the electrodes an integralpart of the housing of the device, or in very close proximity of thedevice at the distal end of a very short lead, overcomes the limitationsof having to use a large pulse generator implanted in the trunk of thepatient's body and thereafter having an insulated lead wire tunneledthrough the limbs to an acupuncture point. (It is noted that the use ofa large pulse generator in the body's trunk, with long leads tunneledthrough tissue or blood vessels to the needed acupoint is the currentstate of the art in implanted electroacupuncture art, as evidenced,e.g., in U.S. Pat. No. 7,373,204).

A preferred EA device made in accordance with the teachings of theinvention is thus small, and has a mechanical shape or envelope thatmakes it easy to implant through a small incision made near or at theacupuncture site. The EA device may be configured in various shapes. Oneshape that may be used is configured in disk form, with a diameter of 2to 3 cm, and a thickness of 2-4 mm. Other shapes that could be usedinclude egg-shaped, spherical or semi-spherical, rectangular withrounded corners, key-shaped, and the like. Whatever the shape, once theEA device is implanted, the housing of the EA device, with itsparticular shape, helps anchor the device, and more importantly helpsanchor its electrodes, in their desired position at or near the targetacupoint that is to be stimulated.

A preferred application for an EA device made in accordance with theteachings presented herein is to treat cardiovascular disease, and moreparticularly heart failure, coronary artery disease (CAD), myocardialischemia, and angina. Thus, the description that follows describes inmuch more detail an EA device that is especially suited to be used totreat cardiovascular disease. However, it is to be understood that theinvention is not limited to treating cardiovascular disease. Asexplained in more detail below, the essence of the invention recognizesthat an electroacupuncture modulation scheme need not be continuous,thereby allowing the implanted EA device to use a small, high density,power source to provide such non-continuous EA modulation. (Here, itshould be noted that “EA modulation,” as that phrase is used herein, isthe application of electrical stimulation pulses, at low intensities,low frequencies and low duty cycles, to at least one of the acupuncturesites that has been identified as affecting a particular illness,deficiency or condition.) As a result, the EA device can be very small.And, because the electrodes form an integral part of the housing of theEA device, or are connected thereto through a very short lead, the EAdevice may thus be implanted directly at (or very near to) the desiredacupoint. Hence, any condition of a patient that has heretofore beensuccessfully treated through conventional acupuncture treatments is apotential candidate for treatment with the EA device described herein.

Modulation (i.e., EA stimulation) regimes, of course, may need to betailored to the specific illness, condition or deficiency being treated,but the same basic approach may be followed as is taught herein forwhatever acupoint is to be modulated. In summary, and as explained morefully below in conjunction with the description of the treating heartfailure, CAD, myocardial ischemia, and/or angina, the basic approach ofEA stimulation includes: (1) identify an acupoint(s) that may be used totreat or mediate the particular illness, condition or deficiency thathas manifest itself in the patient; (2) implant an EA device, made asdescribed herein, so that its electrodes are firmly anchored and locatedso as to be near or on the identified acupoint(s); (3) apply EAmodulation, having a low intensity, low frequency, and low duty cyclethrough the electrode(s) of the EA device so that electrical stimulationpulses flow through the tissue at the acupoint(s) following a prescribedstimulation regimen over several weeks or months or years. At any timeduring this EA stimulation regimen, the patient's illness, condition ordeficiency may be evaluated and, as necessary, the parameters of the EAmodulation applied during the EA stimulation regimen may be adjusted ortweaked in order to improve the results obtained from the EA modulation.

Conditions Treated

As indicated previously, cardiovascular disease is an umbrella term fora variety of diseases affecting the heart. Cardiovascular diseaseincludes any of a number of specific diseases that affect the heartitself and/or the blood vessel system, especially the veins and arteriesleading to and from the heart. For purposes of this patent application,the cardiovascular diseases best treated by the EA device describedherein, and the methods of using such EA device, are focused on thefollowing conditions:

(1) heart failure;

(2) coronary artery disease (also sometimes referred to as coronaryheart disease, and abbreviated as “CAD” or “CHID”);

(3) myocardial ischemia; and

(4) angina.

Each of these four conditions is described in more detail in theparagraphs that follow.

The first of the cardiovascular conditions treated by the device andmethods described herein is heart failure. Heart failure develops inresponse to an insult resulting in a decline in the pumping capacity ofthe heart. (Note, an “insult” in medical terms is a bodily injury,irritation, or other trauma.) In response to the decline in pumpingcapacity, compensatory neurohumoral mechanisms are activated. Amongothers, the Sympathetic Nervous System (SNS), the Renin AngiotensinAldosterone System (RAAS), and the Cytokine System, are activated.Sympathetic nervous system activation has been associated withprogression of heart failure, increased sudden death risk, and increasedmortality. Initially, these neurohumoral mechanisms are able tocompensate for the depressed heart function and maintain hemodynamicstability. However, long-term activation of these neurohumoralmechanisms has deleterious effects on cardiac structure and performance,leading to cardiac decompensation and heart failure progression. Heartfailure patients with the greatest sympathetic activation have the worstprognosis. Pharmacologic treatment of heart failure is focused oninterruption of this sympathetic activation with stability orimprovement in cardiac function and decreased mortality.

The role of increased sympathetic activity in the progression of heartfailure is well understood. The most heightened sympathetic activity ispositively associated with the worst prognosis in heart failure. Thus,the normalization of sympathetic activity is a target in the treatmentof heart failure. International guidelines for the treatment of heartfailure and myocardial infarction focus on reducing the severity of theneurohumoral activation. The benefits of beta-blocker therapy, forexample, as a pharmaceutical targeting inhibition of the SNS, isconsidered a worthwhile treatment to attenuate the progression of heartfailure.

Heart failure means that the heart is unable to pump enough blood tomeet the needs of the body. In addition to hypertension, coronary arterydisease (CAD)—the narrowing of the arteries in the heart—may lead toheart failure. The narrowed arteries may limit the heart's supply ofoxygen rich blood resulting in weakened heart muscles. Most commonly thenarrowing is caused by plaque buildup on (or, atherosclerosis of) thecoronary arteries. As a result of the narrowing and limited blood supplyto the heart (characterized as myocardial ischemia), chest pain calledangina often results. A complete blockage can cause a myocardialinfarction (a heart attack).

In a small study of 20 patients with advanced heart failure whounderwent acute mental stress testing to examine changes in sympatheticactivity associated with that stress, those patients who underwentactive acupuncture treatment did not have increased sympathetic activityafter acupuncture and mental stress testing, unlike the control groupwho experienced a 25% increase. Middlekauff H R, Yu J L, Hui K, et al.:“Acupuncture inhibits sympathetic activation during mental stress inadvanced heart failure patients,” J Cardiac Failure: 8:399-406 (2002).

Additionally, acupuncture in hypertensive patients and its effect onsympathetic activity is also suggestive of utility in heart failure.See, e.g., Longhurst J C: “Acupuncture's beneficial effects on thecardiovascular system,” Prev Cardiol: 1:21-33 (1998).

The second of the cardiovascular conditions treated by the device andmethods described herein is coronary artery disease (also sometimesreferred to as coronary heart disease, and abbreviated as “CAD” or“CHD”, respectively). The current science in acupuncture suggests thatthe mechanism of acupuncture therapy for CAD involves improvement in theneurohumoral regulation, the increase of coronary blood flow andmyocardial oxygen supply, and the reduction of myocardial oxygenconsumption, thereby improving myocardial ischemia.

In a Japanese study, three patients with coronary artery disease whowere treated by acupuncture at PC6 had a decrease in angina episodesduring workload and an improvement in clinical symptoms. Oka, T., Y.Tsuda, S. Suzuki, R. Aji, S. Kaneya and T. Fujino: “Treatment of anginapectoris with acupuncture—role of ‘Neiguan,’” Jpn. J. Oriental Med. 38:85-88 (1987, in Japanese).

In another Japanese study, the measured effect of acupuncture oncoronary artery dilatation during coronary angiography was 68% of thatproduced by isosorbide dinitrate. Kurono Y, Egawa M, Yana T, Shimoo K:“The effect of acupuncture on the coronary arteries as evaluated bycoronary angiography: a preliminary report,” Am J Chin Med 30: 387-396(2002).

In patients who underwent coronary artery bypass grafting in coronaryartery disease, acupuncture applied at HT7 and PC6 increased cardiacoutput and improved heart function better than in the control group,which used drugs only. Lin D, Lin Y, Hu J, Ruan X: “Effect ofElectroacupuncture on Neiguan and Shenmen Points on heart function aftercoronary artery bypass grafting in coronary heart disease.” ModernJournal of Integrated Traditional Chinese and Western Medicine:18:2241-41. Abstract. (2009).

The third of the cardiovascular conditions treated by the device andmethods described herein is myocardial ischemia. In animals, acupuncturehas been shown to reduce electrocardiogram (ECG) evidence of myocardialischemia while improving regional wall motion. See, Li P, Pitsillides KF, Rendig S V et al: “Reversal of reflex-induced myocardial ischemia bymedian nerve stimulation: a feline model of electroacupuncture,”Circulation 97: 1186-94 (1998); Longhurst J C: “Central and peripheralneural mechanisms of acupuncture in myocardial ischemia,” Intl CongressSeries 1238:79-87(9) (2002). Various animal studies have shownimprovement of experimental myocardial ischemia by the acupuncture orelectroacupuncture of PC6 (sometimes alone but more often alongsideother acupoints) Liu X Q, Lu S Q, Luo L: “Influence of acupuncture onepicardial monophasic action potential in vivo in dog with myocardialinfarction,” Tianjin Journal of Traditional Chinese Medicine 22: 480-481(2005).

Additionally, in a randomized controlled trial, electroacupuncture hasbeen shown to alleviate cardiac ischemia-repurfusion injury in adultpatients undergoing heart valve replacement surgery. Yang L, Yang J,Wang Q, et al.: “Cardioprotective effects of electroacupuncturepretreatment on patients undergoing heart valve replacement surgery: arandomized controlled trial,” Ann Thorac Surg 89:781-6 (2010).Electroacupuncture was performed bilaterally at acupoints PC6, LU7, andLU2 once a day for 30 minutes over the five days preceding valvesurgery. It is unclear what mechanism underlies these positive results;however, it may corroborate other research suggesting reduced oxygendemand.

The fourth of the cardiovascular conditions treated by the device andmethods described herein is angina. In one of the first randomizedtrials to compare the effectiveness of acupuncture and sham acupuncturein patients with severe, stable angina pectoris resistant to medicaltreatment, Ballegaard et. al showed that the active treatment group hadsignificantly higher dPRP and higher maximal PRP (note: “dPRP” is thedifference in pressure rate-product between rest and maximum exercise;“PRP” is the pressure-rate product), which was interpreted as anincrease in cardiac functional capacity. Ballegaard S, Jensen G,Pedersen F et al: “Acupuncture in severe, stable angina pectoris: arandomized trial,” Acta Med Scand 220: 307-13 (1986). The investigatorssuggested that the change was caused by a decreased workload secondaryto systemic vasodilation specific to the acupoints and not at the spinalcord level. The acupuncture was bilateral and manual applied at PC6,ST36, and UB14 (aka BL14).

In another study by Richter et al, individualized acupuncture was doneon patients with stable angina with success. Richter A, Herlitz J,Hjalmarson A: “Effect of acupuncture in patients with angina pectoris,”Eur Heart J: 12:175-8 (1991). The maximum workload until onset of chestpain was significantly increased. However, not much difference wasobserved in exercise capacity in comparison to the placebo therapy atthe end of the acupuncture period. Investigators concluded some reliefof myocardial ischemia, possibly by influencing coronary perfusion.While the acupuncture was individualized, five main points were used:PC6, HT5, UB15, UB20 and ST36; and, some additional points include HT7,L14, LI11, and LV3.

Locations Stimulated

For treating any of the four cardiovascular disease conditionspreviously identified—heart failure, coronary artery disease (CAD)(which may also be referred to as coronary heart disease, or CHD),myocardial ischemia, and angina—the preferred acupoints that need to bestimulated by the EA device, i.e., the preferred target tissue locationsat which electrical stimulation should be applied in accordance with aspecified stimulation regimen, include at least one acupoint selectedfrom the following group of nine acupoints, (or their underlying nerves,shown in brackets):

1. PC6 (Neiguan) [median nerve];

-   -   2. ST36 (Zusanli) [deep peroneal nerve];    -   3. BL14 (Jueyinshu), also referred to as UB14 (Jueyinshu)        [4^(th) and 5^(th) thoracic nerve];    -   4. EX-HN1 (Sishencong) (one cm from GV20 (Baihui)) [near        occipital nerve]    -   5. HT7 (Shenmen) [ulnar nerve];    -   6. HT5 (Tongli) [ulnar nerve];    -   7. LI11 (Quchi) [radial nerve];    -   8. LU2 (Yunmen) [anterior thoracic nerve]; and    -   9. LU7 (Lieque) [radial nerve].

The location of the above acupoints may be briefly summarized as: PC6 inthe right or left wrist; ST36 on the anterior aspect of the left orright leg; on the tibialis anterior muscle; BL14 (also known as UB14,Jueyinshu) in the upper back region; EX-HN1 (one cm from Baihui GV20, onthe top of the head); HT7 on the anteromedial aspect of the right orleft wrist, radial to the flexor carpi ulnaris tendon, on the palmarwrist crease; HT5 on the anteromedial aspect of the forearm, radial tothe flexor carpi ulnaris tendon; LI11 on the lateral aspect of theelbow; LU2 on the anterior thoracic region, in the depression of theinfraclavicular fossa; and LU7 on the radial aspect of the forearm,between the tendons of the abductor pollicis longus and the extensorpollicis brevis muscles. All of these acupoints are illustrated anddescribed on pages 25, 26, 29, 33, 39, 45, 64, 81, 84, 85, 99, 106, 154,203 and 213 of WHO Standard Acupuncture Point Locations 2008, previouslyincorporated herein by reference. Selected portions of WHO StandardAcupuncture Point Locations 2008, including pages 25, 26, 29, 33, 39,45, 64, 81, 84, 85, 99, 106, 154, 203 and 213 are included in AppendixD, as are three pages from another reference, Quirico P E, Pedrali T.Teaching Atlas of Acupuncture, Volume 1: Channels and Points. GeorgThieme Verlag. 2007; pages 184, 186 and 190 that further illustrate thelocation of acupoint GV20. Pages 180 through 196 of this Teaching Atlasof Acupuncture book by Quirico and Pedrali are incorporated herein byreference.

In some instances, it will be advantageous to stimulate a plurality (twoor more) of acupoints together, i.e., implant a plurality of EA devices.For example, the acupoints PC6, LU7 and LU2 may be a good candidate fortreating myocardial ischemia with a plurality of EA devices. Also,stimulation can be done bilaterally, i.e., two EA devices may beimplanted, one at, e.g., acupoint PC6 in the right wrist, and one atacupoint PC6 in the left wrist.

Advantageously, the electrode(s) used with the EA device may be eitherintegrated into the housing of the EA device, or located at the distalend of a very short lead (often referred to as a “pigtail” lead) orshort boom that is attached to the housing of the EA device. Electrodesthus fashioned allow the form and shape of the EA housing itself to helpanchor the electrodes in their desired position over, around, near or onthe selected acupoint(s).

Operation of the EA device is simple and straightforward. Once implantedand activated, electrical stimulation pulses are applied to the desiredacupoint at a low intensity, low frequency and low duty cycle inaccordance with a pre-programmed stimulation regimen. Because thestimulation is done at low intensities (amplitudes), low frequencies,and low duty cycles, the power source employed in the implantable EAdevice can also be very small, and can operate for long periods withoutneeding to be replaced, recharged or replenished.

Advantageously, when the power source carried in the EA device has rundown, the entire EA device may be easily replaced through a simplesurgical procedure that is typically no more invasive than removing awart. Alternatively, in some embodiments of the invention, the powersource carried in the EA device may be recharged or replenished in 20 to30 minutes or less, thus providing operating power for the EA device forseveral additional weeks or months before needing to be recharged orreplenished again.

Support for Selected Acupoints

Various studies and research have provided support for using one or moreof these particular nine acupoints for treating heart failure, CAD,myocardial ischemia or angina. A summary of some of these studies andresearch is presented in the paragraphs that follow.

Sishencong (EX-HN).

Sishencong (EX-HN) is not a single point, but is a set or array of fouracupoints, all located about one centimeter away from acupoint GV20 onthe top of the head. For the acupoint(s) Sishencong (EX-HN), a study ofnine healthy people showed that manual acupuncture applied 2 mm deep atthe Sishencong acupoints located on the vertex of the head resulted inan increased high frequency percentage and decreased low frequencypercentage of cardiac vagal and suppressed sympathetic activity,respectively. Wang J D, Kuo T, Yang C: “An alternative method to enhancevagal activities and suppress sympathetic activities in humans,”Autonomic Neuroscience: Basic and Clinical 100: 90-95. (2002). Inanother study in 20 normal male volunteers, manual acupuncture atSishencong was performed with similar success. Also, baroreceptor reflexwas improved, which also suggests increased vagal and decreasedsympathetic activity. Wang J D, “Manual Acupuncture of Sishencong PointsEnhances Cardiac Vagal but Suppresses Cardiovascular SympatheticActivities in Humans.” URN etd-0729105-182922-61 (1998). [Seewww.etd.library.tcu.edu. Abstract Accessed Aug. 16, 2012.] TheSishencong points in acupuncture have historically been used to treatinsomnia. Xie, L., Xie, L., Dong, X.: “124 cases of dyssomnia treatedwith acupuncture at sishencong points,” J. Tradit. Chin. Med. 14,171-173 (1994). Since people with high vagal and low sympatheticactivity have a tendency to sleep, and since the Sishencong acupointsmay be effective in treating insomnia, it was hypothesized that themechanism of action relates to increased vagal and reduced sympatheticactivity, which may be applied to other states of increased sympatheticactivity and improvement of cardiovascular health.

Jueyinshu (BL14).

In a study published in Chinese, two groups of patients with coronaryartery disease were needled at either BL14 and CV14 or BL15 and CV17. Inboth groups the patients' condition of myocardial ischemia improved, butin the former group it was more pronounced. Han Y, Zhang P, Ning M, etal.: “Influence of needling with the combination of back-shu andfront-mu points in the heart and pericardium meridian on theelectrocardiography of patients with coronary heart disease,” ChineseAcupuncture and Moxibustion June 1994. Abstract. (1994).

Shenmen (HT7).

In a study published in Chinese, electroacupuncture was performed oneither HT7 or 517 in two different groups of rabbits with experimentalacute myocardial ischemia. Cai R L, Hu L, Zhou Y P, Wu Z J, Wang K M,Tang X M, Li M, Lu Z H: “Effects of electroacupuncture of “Shenmen” (HT7) and “Zhizheng” (SI 7) on cardiac function and electrical activitiesof cardiac sympathetic nerve in acute myocardial ischemia rabbits,” ZhenCi Yan Jiu. 2007; 32(4): 243-6. Abstract (2007). Changes of heart rate,maximum rising rate and maximum descending rate of the left ventricularsystolic pressure, and discharged of the cardiac sympathetic nerve wererecorded. It was found that electroacupuncture of both HT7 and S17 canimprove cardiac function and electrical activity of the cardiacsympathetic nerve in this acute myocardial ischemia model, and that theeffects of HT7 are markedly better than S17. Additionally, in a ratmodel of gastric distension for which cardiovascular responses wereexamined, electroacupuncture at HT6 and HT7 significantly decreased thepressor response by 44%. Zhou W, Fu L W, Tjen-A-Looi S C, et al.:“Afferent mechanisms underlying stimulation modality-related modulationof acupuncture-related cardiovascular responses,” J Appl Physiol 2005;98:872-880 (2005).

Tongli (HT5).

In a study examining heart rate variability in healthy subjects,acupuncture at HT7 or HT7 and HT5 produced improvement in heart ratevariability suggestive of improved sympathetic tone. Yang Y F, Chou C Y,Li T C, Jan Y M, Tang N Y, Hsieh C L.: “Different effects of acupunctureat shenmen (HT7)-Tongli (HT5) and Shenmen-Neiguan (PC6) points on heartrate variability in healthy subjects.” J Chin Med. 2009; 20(3,4): 97-106(2009).

Neiguan (PC6).

A body of evidence exists that shows the depressor effect on sympatheticactivity of needling or electroacupuncture at PC6 (Neiguan). See, e.g.,Li P and Longhurst J C, “Neural Mechanism of Electroacupuncture'sHypotensive Effects,” Autonomic Neuroscience: Basic & Clinical 157:24-30(2010). Since pharmacologic treatment of heart failure is focused on thenormalization of sympathetic activity, such evidence for the treatmentof hypertension also underlies EA stimulation for the treatment ofcardiovascular diseases. In addition, there are some, mostly Chinese,studies wherein acupuncture or electroacupuncture is performed at PC6(Neiguan) in coronary artery disease and angina. Xiao-min T, Ling Hu,Ke-ming L.: “Experimental study on electroacupuncture in “Neiguan” (PC6)on congestive heart failure rats model and its effect of AngII, ET,CGRP,” Journal of Chengdu University of Traditional Chinese Medicine.January 2007. Abstract (2007); Xu F H, Wang J M: “Clinical observationon acupuncture combined with medication for intractable anginapectoris,” Zhongguo Zhen Jiu. 25(2): 89-91, Abstract (2005). Further, ina study published in Chinese, acupuncture at Neiguan was shown toregulate and improve heart rate variability in 20 coronary heart diseasepatients; this was evidenced by the LF/HF ratio. Shi X, Wang Z P, Liu KX. “Effect of acupuncture on heart rate variability in coronary heartdisease patients,” Zhongguo Zhong Xi Yi Jie He Za Zhi 15(9): 536-8.Abstract (1995).

Zusanli (ST36).

Similar to PC6 (Neiguan), ST36 (Zusanli) is a common point, often usedamongst six or so other points, to affect the cardiovascular system.While it is frequently used alongside many points, its uniqueassociation with positive results for regulation of sympathetic activitysuggests it is a key point. A small study which examines the use of ST36for reduction of blood pressure with success is published by Chiu et al.(1997). Chiu Y J, Chi A, Reid I A et al.: “Cardiovascular and endocrineeffects of acupuncture in hypertensive patients,” Clin. Exp. Hypertens19(7), 1047-1063 (1997). It is expected that the same method ofstimulating ST36 manually or electrically and the resulting reductionsin sympathetic activity are applicable to the disease states of coronaryartery disease, angina, heart failure, and myocardial ischemia.Reduction in sympathetic activity will likely benefit these diseasestates outside of the benefit to blood pressure modulation.

Quchi (LI11).

A study was conducted wherein manual acupuncture and transcutaneouselectrical nerve stimulation were applied at LI11 to a hypertensionmodel in patients with some success in reducing blood pressure. YuanhuaW, Guangqu Z, Xingyou L, Lengxing O, Hongmei S, Bangqi W: “Effect ofacupuncture at quchi and taichong on ET and ACE in the blood of thepatient with hypertension and exploration of its efficacy,” ChineseJournal of Integrated Chinese and Western Medicine 24:1080-83 (2004);Wen-jun W, Chao-yang M.: “Clinical Observation on therapeutic effect ofelectroacupuncture at Quchi (LI11) for treatment of essentialhypertension. Chinese Acupuncture and Moxibustion.” 2009: 29. Abstract(2009); Hongxing Z, Tangfa Z, Yueping L: “Control observation onacupuncture of Quchi (LI 11) and Medication in Transient Action ofDecreasing Blood Pressure,” Chinese Acupuncture and Moxibustion.November 2011. Abstract (2011); Jacobsson F, Himmelmann A, Bergbrant Aet al.: “The effect of transcutaneous electric nerve stimulation inpatients with therapy resistant hypertension,” J. Hum. Hypertens.14(12), 795-798 (2000).

Lieuque (LU7).

In a study examining the effect of electroacupuncture at PC6, LU7 andLU2, patients undergoing heart valve surgery had less cardiacischemia-repurfusion injury. Yang L, Yang J, Wang Q, et al.:“Cardioprotective effects of electroacupuncture pretreatment on patientsundergoing heart valve replacement surgery: a randomized controlledtrial,” Ann Thorac Surg 89:781-6 (2010). Like LI11 (Quchi), LU7(Lieuque) overlies the radial nerve. While the evidence supportingstimulation of LU7 alone for cardiovascular benefit is limited, itsposition over the radial nerve and its use in insomnia are factorsindicating it should be included in the group of acupoints whereelectroacupuncture stimulation may be applied to treat cardiovasculardisease, primarily by successfully reducing sympathetic activity.

Yunmen (LU2).

Yunmen (LU2), like its meridian point Lieuque, (LU7), is also used totreat insomnia. Because it is suggested that the mechanism by whichLieuque (LU7) positively effects insomnia is through reduction insympathetic activity, it is believed that Yunmen (LU2) may also have anapplication in cardiovascular health.

To facilitate an understanding of the methods and systems describedherein, an exemplary EA System will next be described in two sections,Section I and Section II. Section I will describe the invention inconnection with the detailed description of FIGS. 17-31, which relate togeneral principles and concepts associated with the invention. SectionII will then provide, in detail, a specific example of the invention inconnection with the description of FIGS. 1-16.

I. General Principles and Concepts

An exemplary EA System 10 will next be described in connection withFIGS. 17-31. First, with respect to FIG. 17, and subsequently withrespect to other figures which show, and the accompanying descriptiondescribes, more details and features associated with the EA System 10are illustrated and described. As has already been indicated, apreferred application of the EA System is to treat cardiovasculardisease. But, as has also previously been indicated, the EA System hasapplicability to treating other conditions, illnesses and deficienciesother than just cardiovascular disease. The scope of the inventionshould be ascertained from the claims.

As seen in FIG. 17, the EA System 10 includes two main components: (1)an External Control Device (ECD) 20 and (2) an ImplantableElectroAcupuncture Device 30, or IEAD 30. (It is noted that in SectionII below, the IEAD is also referred to using the reference numeral 100.Thus, whether it is referred to as the IEAD 30 or the IEAD 100, it isessentially the same or a similar element.) Two versions of the ECD 20are included in FIG. 17. A first is a hand-held electronic device thatincludes a port 211 enabling it to be coupled to a computer, or similarprocessor. A second is a magnet, typically a cylindrical magnet. Twoversions of an IEAD are also included in FIG. 17, either one of whichmay be used. One embodiment (top right of FIG. 17) has an electrode 32that forms an integral part of the case 31 of the IEAD 30; and the otherembodiment (lower right of FIG. 1A) has an electrode 32 that is locatedat the end of a short lead 41 attached to the IEAD 30.

The IEAD 30, in one embodiment, is disc shaped, having a diameter ofabout 2 to 3 cm, and a thickness of about 2 to 4 mm. It is implantedjust under the skin 12 of a patient near a desired acupuncture site.Other shapes and sizes for the IEAD 30 may also be used, as described inmore detail below. The desired acupuncture site is also referred toherein as a desired or target “acupoint.” For reducing heart failure,coronary artery disease (CAD), myocardial ischemia or angina, the targetacupoints of interest include acupoints PC6, ST36, BL14 (also referredto as UB14), EX-HN1 (located approximately one centimeter from GV20),HT7, HT5, LI11, LU2 and LU7.

The IEAD 30 includes an electrode 32 which may take various forms. Atleast a portion of the electrode, in some embodiments, may include arod-like body and a pointed or tapered tip, thereby resembling a needle.Because of this needle-like shape, and because the electrode 32 replacesthe needle used during conventional acupuncture therapy, the electrode32 may also be referred to herein as a “needle electrode”. However, analternate and preferred electrode form to replace a “needle electrode”is a smooth surface electrode, without any sharp or pointed edges.

For the embodiment shown in top right portion of FIG. 17, and for theIEAD 30, the electrode 32 forms an integral part of the housing 31 ofthe IEAD 30, and is located on an underneath side of the IEAD housingapproximately in the center of the housing. As used here, “underneath”means the housing side farthest from the skin layer 12, or deepest inthe body tissue. Other embodiments may incorporate an electrode that isnot centered in the housing 31, and that is not even on the underneathside of the housing, but is rather on an edge of the housing 31.Alternatively, as shown in the bottom right of FIG. 17, the electrode 32may be located at the distal end of a short lead 41, e.g., nominally10-20 mm long, but in some instances it may be up to 50 mm long,implanted with a strain relief loop to isolate movement of the case fromthe electrode. The proximal end of the lead is attached to the IEAD 30along an edge of the IEAD housing 31 or at a suitable connection pointlocated on the underneath side of the IEAD 30. Alternate configurationsfor attaching the proximal end of the lead 41 to the IEAD housing 31 areillustrated in Appendix F.

When implanted, the IEAD 30 is positioned such that the electrode 32resides near, directly over, or on, the desired acupoint. For thoseembodiments where the electrode 32 forms an integral part of the housing31 of the IEAD 30, there is thus no need for a long lead that must betunneled through body tissue or blood vessels in order to place theelectrode at the desired acupoint. Moreover, even for those embodimentswhere a very short lead may be employed between the IEAD 30 and theelectrode 32, the tunneling required, if any, is orders of magnitudeless than the present state of the art. In fact, with an electrode leadof between 20 mm and 50 mm in length, it is probable that no tunnelingwill be required. Further, because the electrode either forms anintegral part of the IEAD housing 31, or is attached to the IEAD housingusing a very short pigtail lead, the entire IEAD housing 31 serves as ananchor to hold or secure the electrode 32 in its desired location.

For the embodiment depicted in the top right of FIG. 17 and as mentionedabove, the electrode 32 is located in the center of the underneath sideof the IEAD 30. As explained in more detail below, this positioning ofthe electrode 32 is only exemplary, as various types of electrodes maybe employed, as well as various numbers of electrodes and relativepositioning. See, e.g., FIGS. 20 through 21C, and accompanying text,presented below. See also Appendix A and Appendix B.

Still referring to FIG. 17, the EA System 10 also includes an externalcontrol unit, or ECD, 20. The role that the ECD 20 plays in theoperation of the EA system varies as a function of which embodiment ofthe EA System is being used. A USB port 211, located on one side of theECD, allows it to be connected to a PC or notebook computer fordiagnostic, testing, or programming purposes. Other ports or connectorsmay also be used on the ECD 20, as needed by the various embodimentsemployed. In its simplest form, however, the ECD 20 may take the form ofa handheld magnet, described in more detail below in conjunction with aspecific example of the invention.

FIG. 18 is a Table that highlights the main embodiments of the EA System10, and provides a summary description of the functions performed by theExternal Controller 20 and IEAD 30 in each embodiment. It is importantto note that the list of embodiments identified in FIG. 18 is not acomplete list, but is only representative of four of the manyembodiments that could be employed. Thus, the embodiments highlighted inFIG. 18 include, but are not limited to:

Embodiment I

Embodiment I comprises a fully implantable EA System wherein the IEAD 30provides the desired stimulation as controlled by an internal program,or stimulation regime, programmed into its circuits. When thusconfigured, the External Controller 20 is used in Embodiment I only as aprogrammer to program the operating parameters of the IEAD 30. When theIEAD 30 is operating, all of its operating power is obtained from apower source carried within the IEAD 30.

Embodiment II

Embodiment II is essentially the same as Embodiment I except that theExternal Controller 20 is used, when needed, to both program the IEAD 30and to recharge or replenish a rechargeable and/or replenishable powersource carried within the IEAD 30.

Embodiment III

In Embodiment III, all or most all of the functions of the EA System areperformed within the External Controller 20 except for delivery of thedesired stimuli to the desired acupoint through the electrode 32. Hence,when the EA System operates using Embodiment III, the ExternalController 20 must always be present and RF-coupled ormagnetically-coupled to the IEAD 20. That is, in Embodiment III, theExternal Controller 20 generates the stimulation energy at the desiredtime, duration and intensity. Then, it sends, i.e., transmits, thisenergy through the skin 12 to the implantable electroacupuncturestimulator 30. Such transmission of energy through the skin is typicallydone through electromagnetic coupling, e.g., inductive coupling, muchlike a transformer couples energy from its primary coil to its secondarycoil. For coupling through the skin, the primary coil is located in theExternal Controller 20 and the secondary coil is located in the IEAD 30.The IEAD 30 receives this energy and simply passes it on to theelectrode 32 via interconnecting conductive traces or wires. EmbodimentIII is particularly useful for diagnostic and data-gathering purposes,but can also be used by a patient who does not mind occasionally wearingan external device positioned on his or her skin over the location wherethe IEAD is implanted whenever the EA System is operational.

Embodiment IV

In Embodiment IV, the EA system is a fully, self-contained, implantableIEAD except for the use of an external “passive” control element, suchas a magnet. The external control element is used to perform very basicfunctions associated with the IEAD, such as turning the IEAD OFF or ON,changing the intensity of stimulus pulses by a small amount, slightlymodifying the timing of stimulation sessions, resetting the parametersof the stimulation regimen back to default values, and the like.

Next, with reference to FIG. 19, there is shown an illustration orrepresentation of the human body. This illustration shows the locationof effective and ineffective acupoints used in electroacupuncture (EA)for the treatment of various diseases and conditions of a patient,including hypertension, heart failure, CAD, myocardial ischemia orangina. These acupoints have been identified based on research performedby Peng Li and John C. Longhurst, as documented in Li et al., “NeuralMechanism of Electroacupuncture's Hypotensive Effects”, AutonomicNeuroscience: Basic and Clinical 157 (2010) 24-30, which article isincorporated herein by reference. The EA System described hereinutilizes some of the acupoints identified by Li and Longhurst, interalia, as well as other acupoints identified through independentresearch, as being effective for the treatment of heart failure, CAD,myocardial ischemia or angina. According to the Applicants' research,nine such acupoints exist: PC6, ST36, BL14 (also referred to as UB14),EX-HN1 (located approximately one centimeter from GV20), HT7, HT5, LI11,LU2 and LU7.

One stimulation regime stimulates the selected target acupoint overseveral weeks or months, e.g., over a four to eight week stimulationinterval. This four to eight week stimulation interval may then befollowed by, e.g., a two to four week interval of no stimulation. Thenthe cycle begins again: four to eight weeks of stimulation, followed bytwo to four weeks of no stimulation.

Another stimulation regime stimulates the selected target acupoint overseveral months or years, but at a very low duty cycle, e.g., applying astimulation session have a duration of 30 minutes only once or twice aweek. For purposes of the present invention, Applicants have determinedthat if a stimulation session has a duration of T3 minutes, and if thetime between stimulation sessions is T4 minutes, the duty cycle, orratio of T3/T4, should be no greater than 0.05.

One advantage of providing stimulation pulses using a low duty cycle, asdescribed above, is that the power source of the IEAD 30 is able topower operation of the IEAS over long periods of time. Through carefulpower management, detailed more fully below in conjunction with thedescription of a specific example, the IEAD 30 may operate for severalyears.

Turning next to FIGS. 20, 20A and 20B, a mechanical drawing of oneembodiment of the housing 31 of the implantable electroacupuncturestimulator 30 is illustrated, along with various types of electrodesthat may be used therewith. In a first embodiment, as seen in FIG. 20,the housing 31 of the IEAD 30 is preferably disc-shaped, having adiameter “d1” and width “w1”. The housing 31 is made from a suitablebody-tissue-compatible (biocompatible) metal, such as Titanium orstainless steel, having a thickness of 0.2 to 1.0 mm. An electrode 32resides at the center of the underneath side of the housing 31. Theunderneath side of the housing 31 is the side facing out of the paper inFIG. 20, and is the side that is farthest away from the surface of theskin when the stimulator device is implanted in a patient.

The electrode 32 is surrounded by a ceramic or glass section 34 thatelectrically insulates the electrode 32 from the rest of the housing 31.This ceramic or glass 34 is firmly bonded (brazed) to the metal of thehousing 31 to form an hermetic seal. Similarly, a proximal end 35 of theelectrode 34, best seen in the sectional views of FIG. 20A or 20B,passes through the ceramic or glass 34, also forming an hermetic seal.The resultant structure resembles a typical feed-through pin commonlyused in many implantable medical devices, and allows electricalconnection to occur between electrical circuitry housed within thehermetically-sealed housing and body tissue located outside of thehermetically-sealed housing.

In the embodiment of the housing 31 shown in FIGS. 20, 20A and 20B, theelectrode 32 is shown formed to have a narrow tip, much like a needle.Hence, the electrode 32 is sometimes referred to as a needle electrode.It is commonly taught that a needle electrode of this type generallyallows the electric fields associated with having a current flowing outof or into the needle tip to be more sharply focused, and thereby allowsthe resultant current flow through the body tissue to also be moresharply focused. This helps the electrical stimulation to be appliedmore precisely at the desired acupuncture point. Further, because mostacupoints tend to exhibit a lower resistance than do non-acupoints, theamount of power required to direct a stimulation current through theacupoint is lower, thereby helping to conserve power.

However, as will be explained in more detail below in conjunction withApplicant's specific example (Section II), Applicant's preferredelectrode shape is smooth, and symmetrical, which shape andconfiguration allow the resultant electric fields to deeply penetrateinto the desired target tissue.

As is known in the art, all electrical stimulation requires at least twoelectrodes, one for directing, or sourcing, the stimulating current intobody tissue, and one for receiving the current back into the electroniccircuitry. The electrode that receives the current back into theelectronic circuit is often referred to as a “return” or “ground”electrode. The metal housing 31 of the IEAD 30 may function as a returnelectrode during operation of the IEAD 30.

FIG. 20A is a sectional view, taken along the line A-A of FIG. 20, thatshows one embodiment of the IEAD housing wherein the needle electrode 32resides in a cavity 37 formed within the underneath side of the IEADhousing 31.

FIG. 20B is a sectional view, taken along the line A-A of FIG. 20, andshows an alternative embodiment of the underneath side of the IEADwherein the needle or other electrode 32 forms a bump that protrudes outfrom the underneath surface of the IEAD a short distance.

FIG. 20C is a sectional view, taken along the line A-A of FIG. 20, andshows yet another alternative embodiment where a short lead 41, having alength L1, extends out from the housing 31. The electrode 32, which maybe formed in many shapes, is located at a distal end of the lead 41. Theshapes of the electrode, for example, may be a ball, cone or taperedcylindrical, ring, bullet shaped or full or half cuffed, with electrodeanchoring features. See, e.g., Appendix F, where various shapedelectrodes at the end of a short pigtail lead are illustrated. Thelength L1 of this short electrode is nominally 10-20 cm, but may extendas long as 50 mm. A proximal end of the lead 41 attaches to the housing31 of the IEAD 30 through a feed-through type structure made of metal 35and glass (or ceramic) 34, as is known in the art.

Next, with reference to FIGS. 21, 21A, 21B, and 21C, there is shown anembodiment of the IEAD 30 that shows the use of four needle electrodesintegrated within the housing 31 of an IEAD 30. The needle electrodes 32have a tip 33 that protrudes away from the surface of the housing 31 ashort distance. A base, or proximal, portion of the needle electrodes 32is embedded in surrounding glass or ceramic 34 so as to form an hermeticbond between the metal and ceramic. A proximal end 35 of the needleelectrode 32 extends into the housing 31 so that electrical contact maybe made therewith. The ceramic or glass 34 likewise forms a metallicbond with the edge of the housing 31, again forming an hermetic bond.Thus, the needle electrodes 32 and ceramic 34 and metal housing 31function much the same as a feed-through pin in a conventionalimplantable medical device housing, as is known in the art. Suchfeed-through pin allows an electrical connection to be establishedbetween electrical circuitry housed within the hermetically-sealedhousing 31 and body tissue on the outside of the hermetically sealedhousing 31.

Having four needle electrodes arranged in a pattern as shown in FIG. 21allows a wide variation of electric fields to be created emanating fromthe tip 33 of each needle electrode 32 based on the magnitude of thecurrent or voltage applied to each electrode. That is, by controllingthe magnitude of the current or voltage at each tip 32 of the fourelectrodes, the resulting electric field can be steered to a desiredstimulation point, i.e., to the desired electroacupuncture (EA) point.

FIG. 21C is a also a sectional view, taken along the line B-B of FIG.21, that shows yet another embodiment of the EA device where theelectrodes comprise small conductive pads 47 at or near the distal endof a flex circuit cable 45 that extends out from the underneath surfaceof the IEAD a very short distance. To facilitate a view of the distalend of the flex circuit cable 45, the cable is shown twisted 90 degreesas it leaves the underneath surface of the IEAD 30. When implanted, theflex circuit cable 45 may or may not be twisted or have a strain reliefloop, depending upon the relative positions of the IEAD 30 and thetarget acupoint to be stimulated. As can be seen in FIG. 21C, at thedistal end of the flex circuit cable 45 the four electrodes 32 arearranged in a square pattern array. Other arrangements of the electrodes32 may also be employed, a linear array, a “T” array, and the like. Manyother alternate electrode configurations are illustrated, e.g., inAppendix A and Appendix B.

While only one or four electrodes 32 is/are shown as being part of thehousing 31 or at the end of a short lead or cable in FIGS. 20 and 21,respectively, these numbers of electrodes are only exemplary. Any numberof electrodes, e.g., from one to eight electrodes, that conveniently fiton the underneath side or edges of an IEAD housing 31, or on a paddlearray (or other type of array) at the distal end of a short lead, may beused. The goal is to get at least one electrode (whether an actualelectrode or a virtual electrode—created by combining the electricfields emanating from the tips of two or more physical electrodes) asclose as possible to the target EA point, or acupoint. When this isdone, the EA stimulation should be more effective.

Next, with reference to FIGS. 22A through 22E, various alternate shapesof the housing 31 of the IEAD 30 that may be used with an EA System 10are illustrated. The view provided in these figures is a side sectionalview, with at least one electrode 32 also being shown in a sidesectional view. In FIGS. 22A through 22D, the electrode 32 iselectrically insulated from the housing 31 by a glass or ceramicinsulator 34. A portion of the electrode 32 passes through the insulator34 so that a proximal end 35 of the electrode 32 is available inside ofthe housing 31 for electrical contact with electronic circuitry that ishoused within the housing 31.

In FIG. 22A, the housing 31 is egg shaped (or oval shaped). A bump orneedle type electrode 32 protrudes a small distance out from the surfaceof the housing 31. While FIG. 22A shows this electrode located more orless in the middle of the surface of the egg-shaped housing, thispositioning is only exemplary. The electrode may be located anywhere onthe surface of the housing, including at the ends or tips of the housing(those locations having the smallest radius of curvature).

In FIG. 22B, the housing 31 of the IEAD 30 is spherical. Again, a bumpor needle-type electrode 32 protrudes out a small distance from thesurface of the housing 31 at a desired location on the surface of thespherical housing. The spherical housing is typically made by firstmaking two semi-spherical housings, or shells, and then bonding the twosemi-spherical housings together along a seam at the base of eachsemi-spherical shell. The electrode 32 may be located at some pointalong or near this seam.

In FIG. 22C, the housing 31 is semi-spherical, or dome shaped. A bump orneedle electrode 32 protrudes out from the housing at a desiredlocation, typically near an edge of the base of the semi-spherical ordome-shaped housing 31.

In FIG. 22D, the housing is rectangular in shape and has rounded edgesand corners. A bump or needle electrode 32 protrudes out from thehousing at a desired location on the underneath side of the housing, oralong an edge of the housing. As shown in FIG. 22D, one location forpositioning the electrode 32 is on the underneath side near the edge ofthe housing.

In FIG. 22E, the housing 31 is key shaped, having a base portion 51 andan arm portion 53. FIG. 22E includes a perspective view “A” and a sidesectional view “B” of the key-shaped housing 31. As shown, the electrode32 may be positioned near the distal end of the arm portion 53 of thehousing 31. The width of the arm portion 53 may be tapered, and all thecorners of the housing 31 are rounded or slanted so as to avoid anysharp corners. The key-shaped housing shown in FIG. 22E, or variationsthereof, is provided so as to facilitate implantation of the IEAD 30through a small incision, starting by inserting the narrow tip of thearm portion 53, and then sliding the housing under the skin as requiredso that the electrode 32 ends up being positioned over, adjacent or onthe desired acupoint.

In lieu of the bump or needle-type electrodes 32 illustrated in FIGS.22A through 22C, a smooth, flat or other non-protruding electrode 32 mayalso be used.

It is to be noted that while the various housing shapes depicted inFIGS. 22A through 22E have a bump or needle-type electrode (and whichcould also be a flat or smooth electrode as noted in the previousparagraph) that form an integral part of the IEAD housing 31, electrodesat the distal end of a short lead connected to the IEAS housing may alsobe employed with any of these housing shapes.

It is also to be emphasized that other housing shapes could be employedfor the IEAD 30 other than those described. For example, reference ismade to the alternate case shapes shown in Appendix E. The inventiondescribed and claimed herein is not directed so much to a particularshape of the housing 31 of the IEAD 30, but rather to the fact that theIEAD 30 need not provide EA stimulation on a continuous basis, but mayoperate using a very low duty cycle, and therefore the power sourcecarried in the IEAD need not be very large, which in turn allows theIEAS housing 31 to be very small. The resulting small IEAD 30 may thenadvantageously be implanted directly at or near the desired acupoint,without the need for tunneling a lead and an electrode(s) over a longdistance, as is required using prior art implantable electroacupuncturedevices. Instead, the small IEAD 30 used with the present inventionapplies its low duty cycle, non-continuous EA stimulation regime at thedesired acupoint without the use of long leads and extensive tunneling,which stimulation regime applies low intensity, low frequency and lowduty cycle stimulation at the designated acupoint over a period ofseveral years in order to slowly but surely modulate and reducecardiovascular disease (or whatever other condition, illness ordeficiency is being treated).

Turning next to FIG. 23, an electrical functional block diagram of theelectrical circuitry and electrical components housed within the IEAD 30and the External Controller 20 is depicted. The functional circuitryshown to the right of FIG. 4 is what is typically housed within the IEAD30. The functional circuitry shown to the left of FIG. 4 is what istypically housed within the External Control Device 20, also referred toas an External Controller 20. How much circuitry is housed within theIEAD 30 and how much is housed within the External Controller 20 is afunction of which embodiment of the EA System 10 is being used.

It is to be noted and emphasized that the circuitry shown in FIG. 23,and in the other figures which show such circuitry, is intended to befunctional in nature. In practice, a person of skill in the electrical,bioelectrical and electronic arts can readily fashion actual circuitsthat will perform the intended functions. Such circuitry may berealized, e.g., using discrete components, application specificintegrated circuits (ASIC), microprocessor chips, gate arrays, or thelike.

As seen in FIG. 23, the components used and electrical functionsperformed within the IEAD 30 include, e.g., a power source 38, an outputstage 40, an antenna coil 42, a receiver/demodulator circuit 44, astimulation control circuit 46, and a reed switch 48. The componentsused and electrical functions performed with the External Controller 20include, e.g., a power source 22, a transmission coil 24, a centralprocessing unit (CPU) 26, a memory circuit 25, a modulator circuit 28and an oscillator circuit 27. The External Controller 20 also typicallyemploys some type of display device 210 to display to a user the statusor state of the External Controller 20. Further, an interface element212 may be provided that allows, e.g., a means for manual interface withthe Controller 210 to allow a user to program parameters, performdiagnostic tests, and the like. Typically, the user interface 212 mayinclude keys, buttons, switches or other means for allowing the user tomake and select operating parameters associated with use of the EASystem 10. Additionally, a USB port 211 is provided so that the ExternalController 20 may interface with another computer, e.g., a laptop ornotebook computer. Also, a charging port 213 (which may also be in theform of a USB port) allows the power source 22 within the ExternalController 20 to be recharged or replenished, as needed.

In operation, the Stimulation Control Circuit 46 within the IEAD 30 hasoperating parameters stored therein that, in combination withappropriate logic and processing circuits, cause stimulation pulses tobe generated by the Output Stage 40 that are applied to at least one ofthe electrodes 32, in accordance with a programmed or selectedstimulation regime. The operating parameters associated with suchstimulation regime include, e.g., stimulation pulse amplitude, width,and frequency. Additionally, stimulation parameters may be programmed orselected that define the duration of a stimulation session (e.g. 15, 30,45 or 60 minutes), the frequency of the stimulation sessions (e.g.,daily, twice a day, three times a day, once every other day, etc.) andthe number of continuous weeks a stimulation session is applied,followed by the number of continuous weeks a stimulation session is notapplied.

The Power Source 38 within the IEAD 30 may comprise a primary battery, arechargeable battery, a supercapacitor, or combinations or equivalentsthereof. For example, one embodiment of the power source 38, asdiscussed below in connection with FIG. 7, may comprise a combination ofa rechargeable battery and a supercapacitor.

When describing the power source 38, the terms “recharge”, “replenish”,“refill”, “reenergize”, and similar terms (or variations thereof), maybe used interchangeably to mean to put energy into a depleted reservoirof energy. Thus, e.g., a rechargeable battery when it is run down isrecharged. A supercapacitor designed to hold a large volume ofelectrical charge has its store of electrical charge replenished. Apower source that comprises a combination of a rechargeable battery anda supercapacitor, or similar devices, is reenergized. In other words, asthe stored energy within an EA device is consumed, or depleted, thestore of energy within the EA device, in some embodiments, may bereplenished, or the energy reservoir within the EA device is refilled.In other embodiments, the EA device may simply and easily be replaced.

The antenna coil 42 within the IEAD 30, when used (i.e., when the IEAD30 is coupled to the External Controller 20), receives an ac powersignal (or carrier signal) from the External Controller 20 that may bemodulated with control data. The modulated power signal is received anddemodulated by the receiver/demodulator circuit 44. (Thereceiver/demodulator circuit 44 in combination with the antenna coil 42may collectively be referred to as a receiver, or “RCVR”.) Typically thereceiver/demodulator circuit 44 includes simple diode rectification andenvelope detection, as is known in the art. The control data, obtainedby demodulating the incoming modulated power signal, is sent to theStimulation Control circuit 46 where it is used to define the operatingparameters and generate the control signals needed to allow the OutputStage 40 to generate the desired stimulation pulses.

It should be noted that the use of coils 24 and 42 to couple theexternal controller 20 to the IEAD 30 through, e.g., inductive or RFcoupling, of a carrier signal is not the only way the externalcontroller and IEAS may be coupled together, when coupling is needed(e.g., during programming and/or recharging). Optical or magneticcoupling, for example, may also be employed.

The control data, when present, may be formatted in any suitable mannerknown in the art. Typically, the data is formatted in one or morecontrol words, where each control word includes a prescribed number ofbits of information, e.g., 4 bits, 8 bits, or 16 bits. Some of thesebits comprise start bits, other bits comprise error correction bits,other bits comprise data bits, and still other bits comprise stop bits.

Power contained within the modulated power signal is used to recharge orreplenish the Power Source 38 within the IEAD 30. A return electrode 39is connected to a ground (GRD), or reference, potential within the IEAD30. This reference potential may also be connected to the housing 31(which housing is sometimes referred to herein as the “case”) of theIEAD 30.

A reed switch 48 may be employed within the IEAD 30 in some embodimentsto provide a means for the patient, or other medical personnel, to use amagnet placed on the surface of the skin 12 of the patient above thearea where the IEAD 30 is implanted in order to signal the IEAS thatcertain functions are to be enabled or disabled. For example, applyingthe magnet twice within a 2 second window of time could be used as aswitch to manually turn the IEAD 30 ON or OFF.

The Stimulation Control Circuit 46 used within the IEAD 30 contains theappropriate data processing circuitry to enable the Control Circuit 46to generate the desired stimulation pulses. More particularly, theControl Circuit 46 generates the control signals needed that will, whenapplied to the Output Stage circuit 40, direct the Output Stage circuit40 to generate the low intensity, low frequency and low duty cyclestimulation pulses used by the IEAD 30 as it follows the selectedstimulation regime. In one embodiment, the Control circuit 46 maycomprise a simple state machine realized using logic gates formed in anASIC. In other embodiments, it may comprise a more sophisticatedprocessing circuit realized, e.g., using a microprocessor circuit chip.

In the External Controller 20, the Power Source 22 provides operatingpower for operation of the External Controller 20. This operating poweralso includes the power that is transferred to the power source 38 ofthe IEAD 30 whenever the implanted power source 38 needs to bereplenished or recharged. Because the External Controller 20 is anexternal device, the power source 22 may simply comprise a replaceablebattery. Alternatively, it can comprise a rechargeable battery.

The External Controller 20 generates a power (or carrier) signal that iscoupled to the IEAD 30 when needed. This power signal is typically an RFpower signal (an AC signal having a high frequency, such as 40-80 MHz).An oscillator 27 is provided within the External Controller 20 toprovide a basic clock signal for operation of the circuits within theExternal Controller 20, as well as to provide, either directly or afterdividing down the frequency, the AC signal for the power or carriersignal.

The power signal is modulated by data in the modulator circuit 28. Anysuitable modulation scheme may be used, e.g., amplitude modulation,frequency modulation, or other modulation schemes known in the art. Themodulated power signal is then applied to the transmitting antenna orcoil 24. The external coil 24 couples the power-modulated signal to theimplanted coil 42, where the power portion of the signal is used toreplenish or recharge the implanted power source 38 and the data portionof the signal is used by the Stimulation Control circuit 46 to definethe control parameters that define the stimulation regime.

The memory circuit 25 within the External Controller 20 stores neededparameter data and other program data associated with the availablestimulation regimes that may be selected by the user. In someembodiments, only a limited number of stimulation regimes are madeavailable for the patient to use. Other embodiments may allow the useror other medical personnel to define one or more stimulation regimesthat is/are tailored to a specific patient.

Turning next to FIG. 24, there is shown a functional diagram of anOutput Stage 40-1 that may be used within the IEAD 30 for Embodiment III(See FIG. 18 and accompanying text for a description of Embodiment III).The Output Stage 40-1 is basically a pass-through circuit, wherein theentire IEAD 30 comprises nothing more than an electrode 32 connected toa coil 42-1, all of which is carried within an IEAD housing 31. In someembodiments, some simple passive filtering circuitry 424 may also beused to filter and shape the signal being passed from the coil 42-1 tothe electrode(s) 32. Such a simple IEAD housing 31 allows the mechanicalfunctions of the IEAD 30 (size, implant location, effectiveness of EAstimulation, etc.) to be implanted and fully tested without initiallyincurring the additional expenses associated with a fully functionalIEAD 30.

As indicated in the previous paragraph, the function of the simplifiedIEAD 30 shown in FIG. 24 is to pass the signal received at the antennacoil 42-1 on to the electrode(s) 32. More particularly, a signal burst240, when applied to a coil 24-1 in the External Controller 20, iselectromagnetically (e.g., inductively) coupled to the coil 42-1 withinthe Output Stage 40-1 of the IEAD 30, where it appears as signal burst420. The signal burst 420 received by the implanted coil 42-1 may have adifferent intensity than does the signal burst 240 as a function of thecoupling efficiency between the two coils 24-1 and 42-1, the number ofturns in each coil, and the impedance matching that occurs between thecircuits of the External Controller 20 and the combined load attached tothe Output Circuit 40-1, which combined load includes the implanted coil42-1, the electrode 32 and the body tissue in contact with the electrode32. This different intensity may still be sufficiently controlled by theExternal Controller so that the energy contained within the signal burst420, defined in large part by the envelope of the signal burst 240, issufficient to stimulate the tissue at the desired electroacupuncturesite, or acupoint, thereby producing, over time, the desired therapeuticeffect.

In some embodiments, passive filtering circuitry 424 may also be usedwithin the Output Stage 401 to reconfigure or reshape the energy of thesignal burst 240 into a suitable stimulation pulse 422. This stimulationpulse 422 is then applied to the electrode 32 through a couplingcapacitor C.

As mentioned previously, the Output Stage circuit 40-1 shown in FIG. 24is ideally suited for diagnostic and data gathering purposes.Nonetheless, such embodiment can also be effectively used by a patientwho does not object to wearing an External Controller 20 on his or herwrist or leg when the stimulation sessions associated with use of the EASystem 10 are employed.

FIG. 25A functionally shows a representative Output Stage 40-2 that maybe used when voltage stimulation is applied through the electrode(s) 32to the desired acupoint. As seen in FIG. 25A, a positive voltage source,+V, and a negative voltage source, −V, are selectively and sequentiallyapplied to an electrode 32, through switches SW1 and SW2. A couplingcapacitor is preferably employed to prevent dc current from flowingthrough the electrode 32. If more than one electrode 32 is employed, asingle pair of voltage sources may be selectively connected to eachelectrode using a suitable multiplexer circuit (not shown in FIG. 6A),as is known in the art.

FIG. 25B functionally shows a representative Output Stage circuit 40-3that may be used when current stimulation is applied through theelectrode(s) 32 to the desired acupoint. As seen in FIG. 6B, a positivecurrent source, +I, and a negative current source, −I, are selectivelyapplied to an electrode 32. In some embodiments, the current sourcescomprise independent programmable current sources that can readily beprogrammed to source, or sink, a precise current magnitude, as is knownin the art. Advantageously, use of independent programmable currentsources in this fashion allows, when multiple electrodes 32 are used,precise sharing of the currents in order to steer the electric fieldsemanating from the electrodes in a desired manner. For example, if threeelectrodes 32 were employed, a first of which sources 200 microamps (a)of current, and thus functions as an anode, and a second and third ofwhich each sink 100 a, each thus functioning as cathodes, the resultingelectric fields would make it appear that a virtual electrode existed atsome point along a mid-point line between the second and thirdelectrodes. Such steering of a virtual electrode would thus allow theeffectiveness of the EA stimulation to be adjusted or tuned, whicheffectiveness is largely a function of the proximity between theacupoint site and the electrode. Advantageously, this adjustment, ortuning, can occur even after the IEAD 30 is implanted with a fixedphysical location of the electrodes relative to the desired acupointsite.

FIG. 26 illustrates a power source configuration 38-1 that may be usedin some embodiments within the IEAD 30 for the implanted power source38. The power source configuration 38-1 shown in FIG. 26 employs both arechargeable battery 380 and a supercapacitor 382, connected inparallel. The rechargeable battery 380 is charged in conventional mannerusing power received from the recharge circuits. For most embodiments,this would be the power received through implanted coil 42 and theReceiver circuit 44 (see FIG. 23). The power stored in the battery 380may thereafter be used to trickle charge the supercapacitor at timeswhen the IEAD 30 is not stimulating body tissue. Then, when there is ademand for a pulse of stimulation current, the energy required for suchpulse may be pulled from the super capacitor in a relatively rapiddischarge mode of operation. Diodes D1 and D2 are used to isolate thesupercapacitor 382 from the battery 380 when the supercapacitor isundergoing a rapid discharge.

Next, with respect to FIGS. 27 and 28, timing diagrams are shown toillustrate a typical stimulation regime that may be employed by the EASystem 10. First, as seen in FIG. 27, the electroacupuncture (EA)stimulation pulses preferably comprise a series of biphasic stimulationpulses of equal and opposite polarity for a defined time period T1seconds. Thus, as seen at the left edge of FIG. 27, a biphasicstimulation pulse 250 comprises a pulse having a positive phase ofamplitude +P1 followed by a negative phase having an amplitude of −P1.(Alternatively, the biphasic stimulation pulse could comprise a pulsehaving a negative phase of amplitude −P1 followed by a positive phase ofamplitude +P1.) Each phase has a duration of T1/2 seconds, or the entirebiphasic pulse has a total duration of T1/2+T1/2=T1 seconds. (Thisassumes the positive phase duration is equal to the negative phaseduration, which is usually the case for a biphasic stimulation pulse.)The rate at which the biphasic pulses occur is defined by the timeperiod T2 seconds. FIG. 27 makes it appear that T2 is approximatelytwice as long as T1. However, this is not necessarily the case. In manystimulation regimes, T2 may be many times longer than T1. For example,the time T1 may be only 20 milliseconds (ms), with each phase being 10ms, but the time T2 may be one second, or 1000 ms, or two seconds (2000ms). The time periods T1 (pulse width) and T2 (pulse rate) are thusimportant parameters that define a preferred stimulation regime. Theratio of T1/T2 defines the duty cycle of the stimulation pulses when thestimulation pulses are being applied.

Still referring to FIG. 27, the next parameter shown is the stimulationsession period, or T3. This is the time over which stimulation pulses ofwidth T1 are applied at a rate T2. The session length T3, for example,may be 15, 30, 45 or 60 minutes, or any other suitable value as selectedby medical personnel for delivery to a specific patient.

The stimulation session, in turn, is also applied at a set rate, asdetermined by the time period T4. Typical times for T4 include 12, 24 or48 hours, or longer, such as one week or two weeks. Thus, for example,if T4 is 24 hrs. T3 is 30 minutes, T2 is 1 second, and T1 is 20 ms, thenbiphasic stimulation pulses having a width of 20 ms are applied onceeach second for a session time of 30 minutes. The session, in turn, isapplied once every 24 hours, or once each day.

It should be noted that bi-phasic stimulation pulses as shown in FIG. 27are not the only type of stimulation pulses that may be used. In SectionII, below, another type of stimulation pulse (a negative-going pulse) isused with the specific example described there. A negative-going pulseis shown in FIG. 15A.

Next, as seen in FIG. 28, several variations of possible stimulationpatterns are illustrated. In the top line of FIG. 28, a fixed ratestimulation sequence is illustrated where a stimulation session, havinga duration of T3 seconds, is applied at a rate defined by time periodT4. If T3 is 30 minutes, and T4 is 24 hours, then the fixed stimulationrate is one stimulation session lasting 30 minutes applied once eachday.

The second line of FIG. 28 shows a stimulation pattern that uses a fixedstimulation rate and a fixed replenishing rate, which rates are thesame, occurring every T4 seconds. A replenishing signal is a signal fromwhich energy is extracted for charging or replenishing the implantedpower source 38. Frequently, the replenishing signal may itself bemodulated with data, so that whenever replenishing occurs, control datamay also be transmitted. This control data can be new data, as when astimulation regime is to be followed, or it can just be the same data asused previously, and it is used just to refresh or re-store the existingcontrol data.

A replenishing signal is illustrated in FIG. 28 as pulses 260, which aredrawn having a higher amplitude than the stimulation session pulses, andwhich have a duration of T6 seconds. It is noted that the time scale inFIG. 28 is not drawn to scale. Thus, whereas as illustrated in FIG. 28the stimulation session time T3 appears to be twice as long as thereplenishment time T6, such is not necessarily the case.

The third line in FIG. 28 shows an example of a replenishment signalbeing generated every T5 hrs, and a stimulation session occurring everyT4 hours. As shown in FIG. 28, T4 is significantly less than T5. Forexample, T5 may be 168 hours (1 week), whereas T4 may be 24 hours, oronce a day.

The last line in FIG. 28 illustrates a manual selection of theoccurrence of a stimulation session and of a replenishment session.Hence, no rate is associated with either of these events. They simplyoccur whenever they are selected to occur. Selection can be made throughuse of the External Controller 20, or in the case of a stimulationsession (where no external recharging power is needed), through use ofthe reed switch 48). One type of manually-triggered stimulation isillustrated below in the flow diagram of FIG. 30.

Turning next to FIG. 29, a flow chart is shown that illustrates a method500 for automatically applying continuous stimulation sessions inaccordance with a prescribed stimulation regimen. Such method 500applies stimulation sessions having a fixed duration of T3 minutes everyT4 minutes. As seen in FIG. 29, such method is carried out by starting astimulation session (block 502). During the stimulation session, theelapsed time is monitored and a determination is made as to whether thetime period T3 has elapsed (block 504). If not (NO branch of block 504),the time monitoring continues. Once the time period T3 has elapsed (YESbranch of block 504), the stimulation session is stopped (block 506).However, even with the stimulation session stopped, time continues to bemonitored (block 508). When the time T4 has elapsed (YES branch of block508) then a determination is made as to whether a Shut Down mode shouldbe entered (block 510). If so (YES branch of block 510), then theapplication of stimulation sessions is stopped (block 512). If not (NObranch of block 510), then a new stimulation session of T3 minutesbegins (block 502), and the process continues. The timing waveformdiagram corresponding to the flow diagram of FIG. 29 is the top waveformin FIG. 28.

A variation of the method 500 depicted in FIG. 29 is to alternate thetime periods of the stimulation session duration, T3, between twodifferent values. That is, T3 is set to toggle between a first value T31for the stimulation session duration and a second value T3₂ for thestimulation session, with the value T31 being used every otherstimulation session. Thus, a time line of the method of treatingcardiovascular disease follows a sequence T3₁-T4-T3₂-T4-T3₁-T4-T3₂-T4- .. . and so on, where T4 is the time period between stimulation sessions.

If such a method is followed of toggling between two values of T3,representative values for T3₁ and T3₂ could be to set T3₁ to a valuethat ranges between 10 minutes and 40 minutes, and to set T3₂ to a valuethat ranges between 30 minutes and 60 minutes.

Similarly, a further variation of this method of treating cardiovasculardisease would be to toggle the value of T4, the time between stimulationsessions, between two values. That is, in accordance with this method,the time T4 would be set to toggle between a first value T4₁ and asecond value T4₂, with the value T4₁ being used after every otherstimulation session. Thus, a time line of this method of treatingcardiovascular disease would follow a sequenceT3-T4₁-T3-T4₂-T3-T4₁-T3-T4₂-T3-T4₁ . . . and so on, where T3 is theduration of the stimulation sessions.

If such method is followed, representative values for T4₁ and T4₂ couldbe to set T4₁ to a value that ranges between 720 minutes [½ day] and10,080 minutes [1 week], and to set T4₂ to a value that ranges between1,440 minutes [1 day] and 20,160 minutes [2 weeks].

Additional variations of these methods of toggling between differentvalues of T3 and T4 are also possible. For example, multiple values ofT3-T3₁, T3₂, T3₃, T3₄, T3₅ . . . T3_(n)- could be set, and then thevalues could be used in sequence, or randomly during successivestimulation sequences. Multiple values of T4 could also be employed, andthe various values of T3 and T4 could be combined together in thesequences followed.

If such methods are used to adjust the values of T3 and T4, care must beexercised to not exceed the maximum duty cycle associated with thepreferred stimulation regimens. That is, the invention requires that theratio of T3/T4 be no greater than 0.05. Thus, if either, or both, T3 andT4 are varied, limits should be placed on the ranges the parameters canassume in order to preserve the desired duty cycle. For example, therange of values within which T3 may be selected is typically between 10minutes and 60 minutes. The ranges of values within which T4 may beselected is normally between about 12 hours and 2 weeks. However, as thevalue of T4 decreases, and the value of T3 increases, a point is reachedwhere the maximum duty cycle could be exceeded. Thus, to prevent themaximum duty cycle from exceeding 0.05, the range of values for T3 andT4 may be specified by setting the time T3, the duration of thestimulation sessions, to be at least 10 minutes but no longer than amaximum value, T3(max). The value of T3(max) is adjusted, as needed, tomaintain the duty cycle, the ratio of T3/T4, at a value no greater than0.05. Thus, T3(max) is equal to 60 minutes if T4, the time periodbetween stimulation sessions is between 1,200 minutes [20 hours] and20,160 minutes [14 days]. However, T3(max) should be set to a value setby the equation T3(max)=0.05*T4 when T4 is between 720 minutes [½ day]and 1,200 minutes [20 hours].

Next, with reference to FIG. 30, there is depicted a flow chart for amethod 520 for manually triggering the application of stimulationsessions. When manual stimulation sessions are triggered, some basicparameters must still be observed. That is, there must be a minimumduration of a stimulation session T3(min), as well as a maximum durationof a stimulation session T3(max). Similarly, there needs to be a minimumtime period T4(min) that separates one stimulation session from another,and a maximum time period T4(max) allowed between stimulation sessionsbefore the next stimulation session is automatically started.Representative values for these parameters are, for example, T3(min)=10minutes, T3(max)=60 minutes, T4(min)=12 hours, and T4(max)=2 weeks.

With the basic operating parameters described above defined, the method520 shown in FIG. 29 proceeds by first determining whether a manualstart command (or trigger signal) has been received (block 522). If not(NO branch of block 522), then a determination is made as to whether thetime T4(max) has elapsed. If it has (YES branch of block 524), then astimulation session is started (block 526). If T4(max) has not elapsed(NO branch of block 524), then the IEAD 30 just keeps waiting for amanual trigger signal to occur (block 522).

If a manual trigger signal is received (YES branch of block 22), then adetermination is made as to whether T4(min) has elapsed (block 523).Only if T4(min) has elapsed (Yes branch of block 523) is a stimulationsession started (block 526). Thus, two consecutive stimulation sessionscannot occur unless at least the time T4(min) has elapsed since the laststimulation session.

During a stimulation session, the circuitry carrying out method 520 alsomonitors whether a manual stop signal has been received (block 528). Ifso (YES branch of block 528), then a determination is made as to whetherthe time T3(min) has elapsed. If not (NO branch of block 529), then thesession continues because the minimum session time has not elapsed. IfT3(min) has elapsed (YES branch of block 529), then the session isstopped (block 532). If a manual stop signal is not received (NO branchof block 528), and if T3(max) has not yet elapsed (NO branch of block530), then nothing happens (i.e., the session continues) until T3(max)has elapsed (YES branch of block 530), at which time the stimulationsession is terminated (block 532).

Still with reference to FIG. 30, once the session is stopped (block532), a determination is made whether the EA stimulation should shutdown (block 534). If so (YES branch of block 534) the stimulationterminates (block 536). If not, then the circuitry goes into a waitingmode where it monitors whether a manual start command is received, orthe time T4(max) elapses, whichever occurs first (blocks 522, 524), andthe next stimulation session is started (block 526). And, the processcontinues.

Thus, it is seen that the method 520 shown in FIG. 30 allows astimulation session to be manually started at any time a manual startcommand is received, providing that at least the time T4(min) haselapsed since the last session. Similarly, the method allows astimulation session to be manually stopped at any time during thestimulation session, providing that at least the time T3(min) haselapsed since the session started. Absent the occurrence of receiving amanual start command, the next session starts automatically afterT4(max) elapses. Similarly, during a stimulation session, absent a stopcommand, the session will stop automatically after the time T3(max) haselapsed.

Next, with reference to FIG. 31, a flow chart is shown that depicts onemethod 600 of using an EA System 10 of the type described herein, orequivalents thereof, to treat cardiovascular disease. It is emphasizedthat the method shown in FIG. 31 is just one of many methods that may beused, and includes steps or actions taken that may not always be needednor desired. (Note that each step in the flow chart shown in FIG. 31 isrepresented by a rectangular (or other shaped) block having a referencenumber assigned to it. Once the action or other activity indicated in astep, or block, of the method is completed, then the method flows to thenext step, or block, in the flow chart. Decision steps are representedby a diamond (4-sided) or hexagonal (6-sided) shape, also having areference number assigned to it.) For example, the method shown in FIG.31 includes three decision steps or blocks, 612, 616 and 620, where,depending on the question being asked, one of two paths or branches mustbe followed. In a simplified version or embodiment of the method,however, these three decision blocks may be eliminated. In suchsimplified method, the method reduces to following the steps shown inblocks 602, 604, 606, 608, 610, 614, 620 and 622, which blocks aredescribed below.

For the method that uses the three decision blocks, as seen in FIG. 31,the method outlined in the flow diagram of FIG. 31 assumes that thecondition, illness or other physiological deficiency (hereafter“Condition”) being treated by the EA system 10 has been identified.Then, the method begins at block 602, which requires identifying thelocation of the appropriate acupoint(s) for treating the Conditionthrough the application of appropriate EA Modulation. Recall that, asused herein, “EA modulation” is the application of electricalstimulation pulses, at low intensities, frequencies and duty cycles, toat least one of the acupuncture sites that has been identified asaffecting a particular illness, deficiency or condition. For treatingcardiovascular disease, the acupoints include PC6, ST36, BL14 (alsoreferred to as UB14), EX-HN1 (located approximately one centimeter fromGV20), HT7, HT5, LI11, LU2 and LU7. Other possible acupoints also exist,as described previously. So, for purposes of completing the stepdescribed at block 602, one of the possible acupoints that could be usedis selected as the target acupoint.

Once the location of the target acupoint to be modulated has beenidentified, the next step (block 604) is to implant the IEAS 30 so thatits electrodes are firmly anchored and located so as to be near or onthe target acupoint. Then, after waiting a sufficient time for healingto occur associated with the implant surgery (block 606), which isusually just a week or two, the next step is to program the IEAD 30 withthe parameters of the selected stimulation regime that is to be followedby the IEAD 30 as it applies EA modulation to the target acupoint (block608). The parameters that define the selected stimulation regime includethe time periods T1, T2, T3, T4, T5 and T6 (described in connection withthe description of FIGS. 27 and 28), the intensity P1 of the stimulationpulses (also described previously in connection with FIG. 27), and thenumber of weeks, k, that EA modulation is to be applied beforemonitoring the Condition to see if improvement has occurred, as well asthe number of weeks, j, that EA modulation should be turned off beforerestarting the same or a new EA Modulation regime.

Once implanted and programmed, EA Modulation begins and continues for aperiod of k weeks (block 610). After k weeks, the patient's Condition,in this case cardiovascular disease, is checked to see if it hasimproved (decision block 612). If YES, the EA Modulation is turned OFFfor a waiting period of j weeks (block 614). After waiting j weeks,while keeping the EA Modulation deactivated, the Condition is againchecked (decision block 616) to see if the condition has returned to itsprevious high blood pressure state, or to see if the improvement madehas lessened or deteriorated (decision block 616). If NOT, that is, ifthe Condition still remains at acceptable levels, then a decision may bemade by medical personnel in consultation with the patient as to whetherthe EA Modulation regime should be repeated in order to further help thepatient's body maintain the Condition at desired levels (decision block620).

If a decision is made to repeat the EA Modulation (YES branch ofdecision block 620), then the EA Modulation parameters are adjusted asneeded (block 622) and the EA Modulation begins again at the targetacupoint, following the programmed stimulation regime (block 610).

If a decision is made NOT to repeat the EA Modulation (NO branch ofdecision block 620), then that means the treatment for the Condition isover and the process stops (block 624). In such instance, the patientmay elect to have the IEAD 30 removed surgically, which is a very simpleprocedure.

Backtracking for a moment to decision block 612, where a decision wasmade as to whether the Condition had improved after the EA Modulationhad been applied for a period of k weeks, if the determination made isthat the Condition had not improved (NO branch of decision block 612),then again, medical personnel in consultation with the patient may makea decision as to whether the EA Modulation regime should be repeatedagain (block 620).

Further backtracking to decision block 616, where a decision was made asto whether, after the j weeks of applying no additional EA Modulation,the Condition had returned to its previous high blood pressure state, orthe improvement had lessened (YES branch of decision block 616), thenagain medical personnel in consultation with the patient may make adecision as to whether the EA Modulation regime should be repeated again(block 620).

In a simplified version of the method depicted in FIG. 31, only thesteps identified at blocks 602, 604, 606, 608, 610, 614, 620 and 622 arefollowed. This method thus reduces to identifying the target acupoint(block 602), implanting the IEAS at the target acupoint (block 604),waiting for the surgery to heal (block 606), programming EA simulationparameters into the IEAS (block 608) (which programming could actuallybe done before implanting the IEAS, if desired), applying EA modulationto the target acupoint for k weeks (block 610), turning off the EAmodulation for j weeks (block 614), adjusting or tweaking the EAstimulation parameters, if needed (block 622), and repeating the cycleover again starting with block 610.

II. Specific Example

With the foregoing as a foundation for the general principles andconcepts of the present invention, a specific example of the inventionwill next be described in connection with a description of FIGS. 1-16.Such specific example teaches one manner in which the general principlesand concepts described above may be applied to one specificelectroacupuncture (EA) device, or IEAD. Although one specific exampleis being described, there are many variations of it that are generallyreferred to in the description of the specific example as “embodiments”.Also, it should be noted that because the description of the specificexample is presented in conjunction with a different set of drawings,FIGS. 1-16, than were used to describe the general principles andconcepts of the invention, FIGS. 17-31, there will be some differencesin the reference numerals used in connection with one set of drawingsrelative to the reference numerals used in connection with the other setof drawings to describe the same or similar elements. However, suchdifferent reference numerals should not be a source of confusion becausethe context of how and where the references numerals are presented willclearly identify what part or element is being referenced.

The EA device of this specific example is an implantable, coin-shaped,self-contained, symmetrical, leadless electroacupuncture (EA) devicehaving at least two electrode contacts mounted on the surface of itshousing. In one preferred embodiment, the electrodes include a centralcathode electrode on a bottom side of the housing, and an annular anodeelectrode that surrounds the cathode. In another preferred embodiment,the anode annular electrode is a ring electrode placed around theperimeter edge of the coin-shaped housing.

The EA device is leadless. This means there are no leads or electrodesat the distal end of leads (common with most implantable electricalstimulators) that have to be positioned and anchored at a desiredstimulation site. Also, because there are no leads, no tunneling throughbody tissue is required in order to provide a path for the leads toreturn and be connected to a tissue stimulator (also common with mostelectrical stimulators).

The EA device is adapted to be implanted through a very small incision,e.g., less than 2-3 cm in length, directly adjacent to a selectedacupuncture site (“acupoint”) known to moderate or effect acardiovascular condition of a patient.

The EA device is easy to implant. Also, it is symmetrical. This meansthat there is no way that it can be implanted incorrectly (unless thephysician puts it in up-side-down, which would be difficult to do giventhe markings on its case). All that need be done is to cut the incision,and slide the device in place through the incision. Once the implantpocket has been prepared, it is as easy as sliding a coin into a slot.Such implantation can usually be completed in less than 10 minutes in anoutpatient setting, or in a doctor's office. Only minor, localanesthesia need be used. No major or significant complications areenvisioned for the implant procedure. The EA device can also be easilyand quickly explanted, if needed.

The EA device is self-contained. It includes a primary battery toprovide its operating power. It includes all of the circuitry it needs,in addition to the battery, to allow it to perform its intended functionfor several years. Once implanted, the patient will not even know it isthere, except for a slight tingling that may be felt when the device isdelivering stimulus pulses during a stimulation session. Also, onceimplanted, the patient can just forget about it. There are nocomplicated user instructions that must be followed. Just turn it on. Nomaintenance is needed. Moreover, should the patient want to disable theEA device, i.e., turn it OFF, or change stimulus intensity, he or shecan easily do so using, e.g., an external magnet.

The EA device can operate for several years because it is designed to bevery efficient. Stimulation pulses applied by the EA device at aselected acupoint through its electrodes formed on its case are appliedat a very low duty cycle in accordance with a specified stimulationregimen. The stimulation regimen applies EA stimulation during astimulation session that lasts at least 10 minutes, typically 30minutes, and rarely longer than 60 minutes. These stimulation sessions,however, occur at a very low duty cycle. In one preferred treatmentregimen, for example, a stimulation session having a duration of 30minutes is applied to the patient just once a week. The stimulationregimen, and the selected acupoint at which the stimulation is applied,are designed and selected to provide efficient and effective EAstimulation for the treatment of the patient's cardiovascular disease.

The EA device is, compared to most implantable medical devices,relatively easy to manufacture and uses few components. This not onlyenhances the reliability of the device, but helps keep the manufacturingcosts low, which in turn allows the device to be more affordable to thepatient. One key feature included in the mechanical design of the EAdevice is the use of a radial feed-through assembly to connect theelectrical circuitry inside of its housing to one of the electrodes onthe outside of the housing. The design of this radial feed-through pinassembly greatly simplifies the manufacturing process. The processplaces the temperature sensitive hermetic bonds used in the assembly—thebond between a pin and an insulator and the bond between the insulatorand the case wall—away from the perimeter of the housing as the housingis hermetically sealed at the perimeter with a high temperature laserwelding process, thus preserving the integrity of the hermetic bondsthat are part of the feed-through assembly.

In operation, the EA device is safe to use. There are no horrificfailure modes that could occur. Because it operates at a very low dutycycle (i.e., it is OFF much, much more than it is ON), it generateslittle heat. Even when ON, the amount of heat it generates is not much,less than 1 mW, and is readily dissipated. Should a component or circuitinside of the EA device fail, the device will simply stop working. Ifneeded, the EA device can then be easily explanted.

Another key feature included in the design of the EA device is the useof a commercially-available battery as its primary power source. Small,thin, disc-shaped batteries, also known as “coin cells,” are quitecommon and readily available for use with most modern electronicdevices. Such batteries come in many sizes, and use variousconfigurations and materials. However, insofar as applicants are aware,such batteries have never been used in implantable medical devicespreviously. This is because their internal impedance is, or has alwaysthought to have been, much too high for such batteries to be ofpractical use within an implantable medical device where powerconsumption must be carefully monitored and managed so that the device'sbattery will last as long as possible, and so that dips in the batteryoutput voltage (caused by any sudden surge in instantaneous batterycurrent) do not occur that could compromise the performance of thedevice. Furthermore, the energy requirements of other active implantabletherapies are far greater than can be provided by such coin cellswithout frequent replacement.

The EA device of this specific example advantageously employspower-monitoring and power-managing circuits that prevent any suddensurges in battery instantaneous current, or the resulting drops inbattery output voltage, from ever occurring, thereby allowing a wholefamily of commercially-available, very thin, high-output-impedance,relatively low capacity, small disc batteries (or “coin cells”) to beused as the EA device's primary battery without compromising the EAdevice's performance. As a result, instead of specifying that the EAdevice's battery must have a high capacity, e.g., greater than 200 mAh,with an internal impedance of, e.g., less than 5 ohms, which wouldeither require a thicker battery and/or preclude the use ofcommercially-available coin-cell batteries, the EA device of the presentinvention can readily employ a battery having a relatively low capacity,e.g., less than 60 mAh, and a high battery impedance, e.g., greater than5 ohms.

Moreover, the power-monitoring, power-managing, as well as the pulsegeneration, and control circuits used within the EA device arerelatively simple in design, and may be readily fashioned fromcommercially-available integrated circuits (IC's) orapplication-specific integrated circuits (ASIC's), supplemented withdiscrete components, as needed. In other words, the electronic circuitsemployed within the EA device need not be complex nor expensive, but aresimple and inexpensive, thereby making it easier to manufacture the EAdevice and to provide it to patients at an affordable cost.

II. A. Definitions

As used herein, “annular”, “circumferential”, “circumscribing”,“surrounding” or similar terms used to describe an electrode orelectrode array, or electrodes or electrode arrays, (where the phrase“electrode or electrode array,” or “electrodes or electrode arrays,” isalso referred to herein as “electrode/array,” or “electrodes/arrays,”respectively) refers to an electrode/array shape or configuration thatsurrounds or encompasses a point or object, such as another electrode,without limiting the shape of the electrode/array or electrodes/arraysto be circular or round. In other words, an “annular” electrode/array(or a “circumferential” electrode/array, or a “circumscribing”electrode/array, or a “surrounding” electrode/array), as used herein,may be many shapes, such as oval, polygonal, starry, wavy, and the like,including round or circular.

“Nominal” or “about” when used with a mechanical dimension, e.g., anominal diameter of 23 mm, means that there is a tolerance associatedwith that dimension of no more than plus or minus (+/−) 5%. Thus, adimension that is nominally 23 mm means a dimension of 23 mm+/−(0.05×23mm=1.15 mm).

“Nominal” when used to specify a battery voltage is the voltage by whichthe battery is specified and sold. It is the voltage you expect to getfrom the battery under typical conditions, and it is based on thebattery cell's chemistry. Most fresh batteries will produce a voltageslightly more than their nominal voltage. For example, a new nominal 3volt lithium coin-sized battery will measure more than 3.0 volts, e.g.,up to 3.6 volts under the right conditions. Since temperature affectschemical reactions, a fresh warm battery will have a greater maximumvoltage than a cold one. For example, as used herein, a “nominal 3 volt”battery voltage is a voltage that may be as high as 3.6 volts when thebattery is brand new, but is typically between 2.7 volts and 3.4 volts,depending upon the load applied to the battery (i.e., how much currentis being drawn from the battery) when the measurement is made and howlong the battery has been in use.

II. B. Mechanical Design

Turing first to FIG. 1, there is shown a perspective view of onepreferred embodiment of an implantable electroacupuncture device (IEAD)100 made in accordance with the teachings disclosed herein. The IEAD 100may also sometimes be referred to as an implantable electroacupuncturestimulator (IEAS). As seen in FIG. 1, the IEAD 100 has the appearance ofa disc or coin, having a top side 102, a bottom side 106 and an edgeside 104.

As used herein, the “top” side of the IEAD 100 is the side that ispositioned closest to the skin of the patient when the IEAD isimplanted. The “bottom” side is the side of the IEAD that is farthestaway from the skin when the IEAD is implanted. The “edge” of the IEAD isthe side that connects or joins the top side to the bottom side. In FIG.1, the IEAD 100 is oriented to show the bottom side 106 and a portion ofthe edge side 104.

Many of the features associated with the mechanical design of the IEAD100 shown in FIG. 1 are the subject of a prior U.S. Provisional patentapplication, entitled “Radial Feed-Through Packaging for An ImplantableElectroacupuncture Device”, Application No. 61/676,275, filed 26 Jul.2012, which application is incorporated here by reference.

It should be noted here that throughout this application, the terms IEAD100, IEAD housing 100, bottom case 124, can 124, or IEAD case 124, orsimilar terms, are used to describe the housing structure of the EAdevice. In some instances it may appear these terms are usedinterchangeably. However, the context should dictate what is meant bythese terms. As the drawings illustrate, particularly FIG. 7, there is abottom case 124 that comprises the “can” or “container” wherein thecomponents of the IEAD 100 are first placed and assembled duringmanufacture of the IEAD 100. When all of the components are assembledand placed within the bottom case 124, a top plate 122 is welded to thebottom case 124 to form the hermetically-sealed housing of the IEAD. Thecathode electrode 110 is attached to the outside of the bottom case 124,and the ring anode electrode 120 is attached, along with its insulatinglayer 129, around the perimeter edge 104 of the bottom case 124.Finally, a layer of silicone molding 125 covers the IEAD housing exceptfor the outside surfaces of the anode ring electrode and the cathodeelectrode.

The embodiment of the IEAD 100 shown in FIG. 1 utilizes two electrodes,a cathode electrode 110 that is centrally positioned on the bottom side106 of the IEAD 100, and an anode electrode 120. The anode electrode 120is a ring electrode that fits around the perimeter edge 104 of the IEAD100. Not visible in FIG. 1, but which is described hereinafter inconnection with the description of FIG. 7, is a layer of insulatingmaterial 129 that electrically insulates the anode ring electrode 120from the perimeter edge 104 of the housing or case 124.

Not visible in FIG. 1, but a key feature of the mechanical design of theIEAD 100, is the manner in which an electrical connection is establishedbetween the ring electrode 120 and electronic circuitry carried insideof the IEAD 100. This electrical connection is established using aradial feed-through pin that fits within a recess formed in a segment ofthe edge of the case 124, as explained more fully below in connectionwith the description of FIGS. 5, 5A, 5B and 7.

In contrast to the feed-through pin that establishes electrical contactwith the anode electrode, electrical connection with the cathodeelectrode 110 is established simply by forming or attaching the cathodeelectrode 110 to the bottom 106 of the IEAD case 124. In order toprevent the entire case 124 from functioning as the cathode (which isdone to better control the electric fields established between the anodeand cathode electrodes), the entire IEAD housing is covered in a layerof silicone molding 125 (see FIG. 7), except for the outside surface ofthe anode ring electrode 120 and the cathode electrode 110.

The advantage of using a central cathode electrode and a ring anodeelectrode is described in U.S. Provisional Patent Application No.61/672,257, filed 6 Mar. 2012, entitled “Electrode Configuration forImplantable Electroacupuncture Device”, which application isincorporated herein by reference. One significant advantage of thiselectrode configuration is that it is symmetrical. That is, whenimplanted, the surgeon or other medical personnel performing the implantprocedure, need only assure that the cathode side of the IEAD 100 isfacing down, i.e., facing deeper into the tissue, and that the IEAD isover the desired acupoint, or other tissue location, that is intended toreceive the electroacupuncture (EA) stimulation. The orientation of theIEAD 100 is otherwise not important.

Implantation of the IEAD is illustrated in FIG. 1A. Shown in FIG. 1A isa limb 80 of the patient wherein an acupoint 90 has been identified thatis to receive acupuncture treatment (in this case electroacupuncturetreatment). An incision 82 is made into the limb 80 a short distance,e.g., 10-15 mm, away from the acupoint 90. A slot 84 (parallel to thearm) is formed at the incision by lifting the skin closest to theacupoint up at the incision. As necessary, the surgeon may form a pocketunder the skin at the acupoint location. The IEAD 100, with its top side102 being closest to the skin, is then slid through the slot 84 into thepocket so that the center of the IEAD is located under the acupoint 90.This implantation process is as easy as inserting a coin into a slot.With the IEAD 100 in place, the incision is sewn or otherwise closed,leaving the IEAD 100 under the skin 80 at the location of the acupoint90 where electroacupuncture (EA) stimulation is desired.

It should be noted that while FIG. 1B illustrates the acupoint 90 asbeing on the surface of the skin, the actual location where acupuncturetreatment (whether it be administered through a needle, or throughelectroacupuncture (EA) stimulation) is most effective for purposes ofthe present invention is at a distance d2 below the skin surface alongan axis line 92 extending orthogonally into the skin from the locationon the skin where the acupoint 90 is indicated as being positioned. Thedistance d2 varies depending upon where the acupoint is located on thebody. The depth d2 where EA stimulation is most effective for purposesof the particular acupoint chosen (to treat a cardiovascular disease)appears to be between about 6 to 10 mm below the acupoint 90 on the skinsurface when the acupoint 90 is located in the forearm (e.g., acupointsPC6, HT5, LI11); and may be much deeper, e.g., 1 to 2 cm, if thelocation of an acupoint 90 is located in the leg (e.g., acupoint ST36).

FIG. 1B shows a sectional view of the IEAD 100 implanted so as to becentrally located under the skin at the selected acupoint 90, and overthe acupoint axis line 92. Although the depth of implantation will varydepending upon the acupoint chosen and the condition to be tested, herethe IEAD 100 is implanted at a depth d1 of approximately 2-4 mm underthe skin. The top side 102 of the IEAD is nearest to the skin 80 of thepatient. The bottom side 106 of the IEAD, which is the side on which thecentral cathode electrode 110 resides, is farthest from the skin.Because the cathode electrode 110 is centered on the bottom of the IEAD,and because the IEAD 100 is implanted so as to be centered under thelocation on the skin where the acupoint 90 is located, the cathode 110is also centered over the acupoint axis line 92.

FIG. 1B further illustrates the electric field gradient lines 88 thatare created in the body tissue 86 surrounding the acupoint 90 and theacupoint axis line 92. (Note: for purposes herein, when reference ismade to providing EA stimulation at a specified acupoint, it isunderstood that the EA stimulation is provided at a depth ofapproximately d2 below the location on the skin surface where theacupoint is indicated as being located.) As seen in FIG. 1B, theelectric field gradient lines are strongest along a line that coincideswith, or is near to, the acupoint axis line 92. It is thus seen that oneof the main advantages of using a symmetrical electrode configurationthat includes a centrally located electrode surrounded by an annularelectrode is that the precise orientation of the IEAD within its implantlocation is not important. So long as one electrode is centered over thedesired target location, and the other electrode surrounds the firstelectrode (e.g., as an annular electrode), a strong electric fieldgradient is created that is aligned with the acupoint axis line. Thiscauses the EA stimulation current to flow along (or very near) theacupoint axis line 92, and will result in the desired EA stimulation inthe tissue at a depth d2 below the acupoint location indicated on theskin.

FIG. 2 shows a plan view of the “cathode” side (or bottom side) of theIEAD 100. As seen in FIG. 2, the cathode electrode 110 appears as acircular electrode, centered on the cathode side, having a diameter D1.The IEAD housing has a diameter D2 and an overall thickness or width W2.For the preferred embodiment shown in these figures, D1 is about 4 mm,D2 is about 23 mm and W2 is a little over 2 mm (2.2 mm).

FIG. 2A shows a side view of the IEAD 100. The ring anode electrode 120,best seen in FIG. 2A, has a width W1 of about 1.0 mm, or approximately ½of the width W2 of the IEAD.

FIG. 3 shows a plan view of the “skin” side (the top side) of the IEAD100. As will be evident from subsequent figure descriptions, e.g., FIGS.5A and 5B, the skin side of the IEAD 100 comprises a top plate 122 thatis welded in place once the bottom case 124 has all of the electroniccircuitry, and other components, placed inside of the housing.

FIG. 3A is a sectional view of the IEAD 100 of FIG. 1 taken along theline A-A of FIG. 3. Visible in this sectional view is the feed-throughpin 130, including the distal end of the feed-through pin 130 attachedto the ring anode electrode 120. Also visible in this section view is anelectronic assembly 133 on which various electronic components aremounted, including a disc-shaped battery 132. FIG. 3A furtherillustrates how the top plate 122 is welded, or otherwise bonded, to thebottom case 124 in order to form the hermetically-sealed IEAD housing100. (Note, in FIG. 3A, the “top” plate 122 is actually shown on theleft side of the “bottom” case 124, which is shown on the right side.This is because the orientation of the drawing in FIG. 3A shows the IEAD100 standing on its edge.)

FIG. 4 shows a perspective view of the IEAD case 124, including thefeed-through pin 130, before the electronic components are placedtherein, and before being sealed with the “skin side” cover plate 122.The case 124 is similar to a shallow “can” without a lid, having a shortside wall around its perimeter. Alternatively, the case 124 may beviewed as a short cylinder, closed at one end but open at the other.(Note, in the medical device industry the housing of an implanted deviceis often referred to as a “can”.) The feed-through pin 130 passesthrough a segment of the wall of the case 124 that is at the bottom of arecess 140 formed in the wall. The use of this recess 140 to hold thefeed-through pin 130 is a key feature of the invention because it keepsthe temperature-sensitive portions of the feed-through assembly (thoseportions that could be damaged by excessive heat) away from the thermalshock and residual weld stress inflicted upon the case 124 when thecover plate 122 is welded thereto.

FIG. 4A is a side view of the IEAD case 124, and shows an annular rim126 formed on both sides of the case 124. The ring anode electrode 120fits between these rims 126 once the ring electrode 120 is positionedaround the edge of the case 124. A silicone insulator layer 129 (seeFIG. 7) is placed between the backside of the ring anode electrode 120and the perimeter edge of the case 124 where the ring anode electrode120 is placed around the edge of the case 124.

FIG. 5 shows a plan view of the empty IEAD case 124 shown in theperspective view of FIG. 4. An outline of the recess cavity 140 is alsoseen in FIG. 5, as is the feed-through pin 130. A bottom edge of therecess cavity 140 is located a distance D5 radially inward from the edgeof the case 124. In one embodiment, the distance D5 is between about 2.0to 2.5 mm. The feed-through pin 130, which is just a piece of solidwire, is shown in FIG. 5 extending radially outward from the case 124above the recess cavity 140 and radially inward from the recess cavitytowards the center of the case 124. The length of this feed-through pin130 is trimmed, as needed, when a distal end (extending above therecess) is connected (welded) to the anode ring electrode 120 (passingthrough a hole in the ring electrode 120 prior to welding) and when aproximal end of the feed-through pin 130 is connected to an outputterminal of the electronic assembly 133.

FIG. 5A depicts a sectional view of the IEAD housing 124 of FIG. 5 takenalong the section line A-A of FIG. 5. FIG. 5B shows an enlarged view ordetail of the portion of FIG. 5A that is encircled with the line B.Referring to FIGS. 5A and 5B jointly, it is seen that the feed-throughpin 130 is embedded within an insulator material 136, which insulatingmaterial 136 has a diameter of D3. The feed-through pin assembly (whichpin assembly comprises the combination of the pin 130 embedded into theinsulator material 136) resides on a shoulder around an opening or holeformed in the bottom of the recess 140 having a diameter D4. For theembodiment shown in FIGS. 5A and 5B, the diameter D3 is 0.95-0.07 mm,where the −0.07 mm is a tolerance. (Thus, with the tolerance considered,the diameter D3 may range from 0.88 mm to 0.95 mm) The diameter D4 is0.80 mm with a tolerance of −0.06 mm. (Thus, with the toleranceconsidered, the diameter D4 could range from 0.74 mm to 0.80 mm).

The feed-through pin 130 is preferably made of pure platinum 99.95%. Apreferred material for the insulator material 136 is Ruby or alumina.The IEAD case 124, and the cover 122, are preferably made from titanium.The feed-through assembly, including the feed-through pin 130,ruby/alumina insulator 136 and the case 124 are hermetically sealed as aunit by gold brazing. Alternatively, active metal brazing can be used.(Active metal brazing is a form of brazing which allows metal to bejoined to ceramic without metallization.)

The hermeticity of the sealed IEAD housing is tested using a helium leaktest, as is common in the medical device industry. The helium leak rateshould not exceed 1×10⁻⁹ STD cc/sec at 1 atm pressure. Other tests areperformed to verify the case-to-pin resistance (which should be at least15×10⁶ Ohms at 100 volts DC), the avoidance of dielectric breakdown orflashover between the pin and the case 124 at 400 volts AC RMS at 60 Hzand thermal shock.

One important advantage provided by the feed-through assembly shown inFIGS. 4A, 5, 5A and 5B is that the feed-through assembly made from thefeed-through pin 130, the ruby insulator 136 and the recess cavity 140(formed in the case material 124) may be fabricated and assembled beforeany other components of the IEAD 100 are placed inside of the IEAD case124. This advantage greatly facilitates the manufacture of the IEADdevice.

Turning next to FIG. 6, there is shown a perspective view of anelectronic assembly 133. The electronic assembly 133 includes amulti-layer printed circuit (pc) board 138, or equivalent mountingstructure, on which a battery 132 and various electronic components 134are mounted. This assembly is adapted to fit inside of the empty bottomhousing 124 of FIG. 4 and FIG. 5.

FIGS. 6A and 6B show a plan view and side view, respectively, of theelectronic assembly 133 shown in FIG. 6. The electronic components areassembled and connected together so as to perform the circuit functionsneeded for the IEAD 100 to perform its intended functions. These circuitfunctions are explained in more detail below under the sub-heading“Electrical Design”. Additional details associated with these functionsmay also be found in many of the provisional patent applicationsreferenced above.

FIG. 7 shows an exploded view of the complete IEAD 100, illustrating itsmain constituent parts. As seen in FIG. 7, the IEAD 100 includes,starting on the right and going left, a cathode electrode 110, a ringanode electrode 120, an insulating layer 129, the bottom case 124 (the“can” portion of the IEAD housing, and which includes the feed-throughpin 130 which passes through an opening in the bottom of the recess 140formed as part of the case, but wherein the feed-through pin 130 isinsulated and does not make electrical contact with the metal case 124by the ruby insulator 136), the electronic assembly 133 (which includesthe battery 132 and various electronic components 134 mounted on a pcboard 138) and the cover plate 122. The cover plate 122 is welded to theedge of the bottom case 124 using laser beam welding, or some equivalentprocess, as one of the final steps in the assembly process.

Other components included in the IEAD assembly, but not necessarilyshown or identified in FIG. 7, include adhesive patches for bonding thebattery 132 to the pc board 138 of the electronic assembly 133, and forbonding the electronic assembly 133 to the inside of the bottom of thecase 124. To prevent high temperature exposure of the battery 132 duringthe assembly process, conductive epoxy is used to connect a batteryterminal to the pc board 138. Because the curing temperature ofconductive epoxy is 125° C., the following process is used: (a) firstcure the conductive epoxy of a battery terminal ribbon to the pc boardwithout the battery, (b) then glue the battery to the pc board usingroom temperature cure silicone, and (c) laser tack weld the connectingribbon to the battery.

Also not shown in FIG. 7 is the manner of connecting the proximal end ofthe feed-through pin 130 to the pc board 138, and connecting a pc boardground pad to the case 124. A preferred method of making theseconnections is to use conductive epoxy and conductive ribbons, althoughother connection methods known in the art may also be used.

Further shown in FIG. 7 is a layer of silicon molding 125 that is usedto cover all surfaces of the entire IEAD 100 except for the anode ringelectrode 120 and the circular cathode electrode 110. An overmoldingprocess is used to accomplish this, although overmolding using siliconeLSR 70 (curing temperature of 120° C.) with an injection molding processcannot be used. Overmolding processes that may be used include: (a)molding a silicone jacket and gluing the jacket onto the case using roomtemperature cure silicone (RTV) inside of a mold, and curing at roomtemperature; (b) injecting room temperature cure silicone in a PEEK orTeflon® mold (silicone will not stick to the Teflon® or PEEK material);or (c) dip coating the IEAD 100 in room temperature cure silicone whilemasking the electrode surfaces that are not to be coated. (Note: PEEK isa well-known semicrystalline thermoplastic with excellent mechanical andchemical resistance properties that are retained at high temperatures.)

When assembled, the insulating layer 129 is positioned underneath thering anode electrode 120 so that the anode electrode does not short tothe case 124. The only electrical connection made to the anode electrode120 is through the distal tip of the feed-through pin 130. Theelectrical contact with the cathode electrode 110 is made through thecase 124. However, because the entire IEAD is coated with a layer ofsilicone molding 125, except for the anode ring electrode 120 and thecircular cathode electrode 110, all stimulation current generated by theIEAD 100 must flow between the exposed surfaces of the anode andcathode.

It is noted that while the preferred configuration described herein usesa ring anode electrode 120 placed around the edges of the IEAD housing,and a circular cathode electrode 110 placed in the center of the cathodeside of the IEAD case 124, such an arrangement could be reversed, i.e.,the ring electrode could be the cathode, and the circular electrodecould be the anode.

Moreover, the location and shape of the electrodes may be configureddifferently than is shown in the one preferred embodiment describedabove in connection with FIGS. 1, and 2-7. For example, the ring anodeelectrode 120 need not be placed around the perimeter of the device, butsuch electrode may be a flat circumferential electrode that assumesdifferent shapes (e.g., round or oval) that is placed on the bottom oron the top surface of the IEAD so as to surround the central electrode.Further, for some embodiments, the surfaces of the anode and cathodeelectrodes may have convex surfaces.

It is also noted that while one preferred embodiment has been disclosedherein that incorporates a round, or short cylindrical-shaped housing,also referred to as a coin-shaped housing, the invention does notrequire that the case 124 (which may also be referred to as a“container”), and its associated cover plate 122, be round. The casecould just as easily be an oval-shaped, rectangular-shaped (e.g., squarewith smooth corners), polygonal-shaped (e.g., hexagon-, octagon-,pentagon-shaped), button-shaped (with convex top or bottom for asmoother profile) device. Some particularly attractive alternate caseshapes, and electrode placement on the surfaces of those case shapes,are illustrated in Appendix E. Any of these alternate shapes, or others,would still permit the basic principles of the invention to be used toprovide a robust, compact, thin, case to house the electronic circuitryand power source used by the invention; as well as to help protect afeed-through assembly from being exposed to excessive heat duringassembly, and to allow the thin device to provide the benefits describedherein related to its manufacture, implantation and use. For example, aslong as the device remains relatively thin, e.g., no more than about 2-3mm, and does not have a maximum linear dimension greater than about 25mm, then the device can be easily implanted in a pocket over the tissuearea where the selected acupoint(s) is located. As long as there is arecess in the wall around the perimeter of the case wherein thefeed-through assembly may be mounted, which recess effectively moves thewall or edge of the case inwardly into the housing a safe thermaldistance, as well as a safe residual weld stress distance, from theperimeter wall where a hermetically-sealed weld occurs, the principlesof the invention apply.

Further, it should be noted that while the preferred configuration ofthe IEAD described herein utilizes a central electrode on one of itssurfaces that is round, having a diameter of nominally 4 mm, suchcentral electrode need not necessarily be round. It could be ovalshaped, polygonal-shaped, or shaped otherwise, in which case its size isbest defined by its maximum width, which will generally be no greaterthan about 7 mm.

Finally, it is noted that the electrode arrangement may be modifiedsomewhat, and the desired attributes of the invention may still beachieved. For example, as indicated previously, one preferred electrodeconfiguration for use with the invention utilizes a symmetricalelectrode configuration, e.g., an annular electrode of a first polaritythat surrounds a central electrode of a second polarity. Such asymmetrical electrode configuration makes the implantableelectroacupuncture device (IEAD) relatively immune to being implanted inan improper orientation relative to the body tissue at the selectedacupoint(s) that is being stimulated. However, an electrodeconfiguration that is not symmetrical may still be used and many of thetherapeutic effects of the invention may still be achieved. For example,two spaced-apart electrodes on a bottom surface of the housing, one of afirst polarity, and a second of a second polarity, could still, whenoriented properly with respect to a selected acupoint tissue location,provide some desired therapeutic results

FIG. 7A schematically illustrates a few alternative electrodeconfigurations that may be used with the invention. The electrodeconfiguration schematically shown in the upper left corner of FIG. 7A,identified as “I”, schematically illustrates one central electrode 110surrounded by a single ring electrode 120. This is one of the preferredelectrode configurations that has been described previously inconnection, e.g., with the description of FIGS. 1, 1A, 1B and 7, and ispresented in FIG. 7A for reference and comparative purposes.

In the lower left corner of FIG. 7A, identified as “II”, anelectrode/array configuration is schematically illustrated that has acentral electrode 310 of a first polarity surrounded by an electrodearray 320 a of two electrodes of a second polarity. When the twoelectrodes (of the same polarity) in the electrode array 320 a areproperly aligned with the body tissue being stimulated, e.g., alignedwith the longitudinal axis of the limb 80 (see FIG. 1A) wherein the IEADis implanted, then such electrode configuration can stimulate the bodytissue at or near the desired acupoint(s) with the same, or almost thesame, efficacy as can the electrode configuration I (upper right cornerof FIG. 7A).

Note, as has already been described above, the phrase “electrode orelectrode array,” or “electrodes or electrode arrays,” may also bereferred to herein as “electrode/array” or “electrodes/arrays,”respectively. For the ease of explanation, when an electrode array isreferred to herein that comprises a plurality (two or more) ofindividual electrodes of the same polarity, the individual electrodes ofthe same polarity within the electrode array may also be referred to as“individual electrodes”, “segments” of the electrode array, “electrodesegments”, or just “segments”.

In the lower right corner of FIG. 7A, identified as “Ill”, en electrodeconfiguration is schematically illustrated that has a centralelectrode/array 310 b of three electrode segments of a first polaritysurrounded by an electrode array 320 b of three electrode segments of asecond polarity. As shown in FIG. 7A-III, the three electrode segmentsof the electrode array 320 b are symmetrically positioned within thearray 320 b, meaning that they are positioned more or less equidistantfrom each other. However, a symmetrical positioning of the electrodesegments within the array is not necessary to stimulate the body tissueat the desired acupoint(s) with some efficacy.

In the upper right corner of FIG. 7A, identified as “IV”, anelectrode/array configuration is schematically illustrated that has acentral electrode array 310 c of a first polarity surrounded by anelectrode array 320 c of four electrode segments of a second polarity.The four electrode segments of the electrode array 320 c are arrangedsymmetrically in a round or oval-shaped array. The four electrodesegments of the electrode array 310 b are likewise arrangedsymmetrically in a round or oval-shaped array. Again, however, whilepreferred for many configurations, the use of a symmetricalelectrode/array, whether as a central electrode array 310 or as asurrounding electrode/array 320, is not required in all configurations.

The electrode configurations I, II, III and IV shown schematically inFIG. 7A are only representative of a few electrode configurations thatmay be used with the present invention. Further, it is to be noted thatthe central electrode/array 310 need not have the same number ofelectrode segments as does the surrounding electrode/array 320.Typically, the central electrode/array 310 of a first polarity will be asingle electrode; whereas the surrounding electrode/array 320 of asecond polarity may have n individual electrode segments, where n is aninteger that can vary from 1, 2, 3, . . . n. Thus, for a circumferentialelectrode array where n=4, there are four electrode segments of the samepolarity arranged in circumferential pattern around a centralelectrode/array. If the circumferential electrode array with n=4 is asymmetrical electrode array, then the four electrode segments will bespaced apart equally in a circumferential pattern around a centralelectrode/array. When n=1, the circumferential electrode array reducesto a single circumferential segment or a single annular electrode thatsurrounds a central electrode/array.

Additionally, the polarities of the electrode/arrays may be selected asneeded. That is, while the central electrode/array 310 is typically acathode (−), and the surrounding electrode/array 320 is typically ananode (+), these polarities may be reversed.

It should be noted that the shape of the circumferentialelectrode/array, whether circular, oval, or other shape, need notnecessarily be the same shape as the IEAD housing, unless thecircumferential electrode/array is attached to a perimeter edge of theIEAD housing. The IEAD housing may be round, or it may be oval, or itmay have a polygon shape, or other shape, as needed to suit the needs ofa particular manufacturer and/or patient.

Additional electrode configurations, both symmetrical electrodeconfigurations and non-symmetrical electrode configurations, that may beused with an EA stimulation device as described herein, are described inAppendix A and Appendix B.

II. C. Electrical Design

Next, with reference to FIGS. 8A-14, the electrical design and operationof the circuits employed within the IEAD 100 will be described. Moredetails associated with the design of the electrical circuits describedherein may be found in the following previously-filed U.S. Provisionalpatent applications, which applications are incorporated herein byreference: (1) Appl. No. 61/626,339, filed Sep. 23, 2011, entitledImplantable Electroacupuncture Device and Method for TreatingCardiovascular Disease; (2) Appl. No. 61/609,875, filed Mar. 12, 2012,entitled Boost Converter Output Control For ImplantableElectroacupuncture Device; (3) Appl. No. 61/672,257, filed Jul. 16,2012, entitled Boost Converter Circuit Surge Control For ImplantableElectroacupuncture Device Using Digital Pulsed Shutdown; (4) Appl. No.61/672,661, filed Jul. 17, 2012, entitled Smooth Ramp-Up StimulusAmplitude Control For Implantable Electroacupuncture Device; and (5)Appl. No. 61/674,691, filed Jul. 23, 2012, entitled Pulse ChargeDelivery Control In An Implantable Electroacupuncture Device.

FIG. 8A shows a functional block diagram of an implantableelectroacupuncture device (IEAD) 100 made in accordance with theteachings disclosed herein. As seen in FIG. 8A, the IEAD 100 uses animplantable battery 215 having a battery voltage V_(BAT). Also includedwithin the IEAD 100 is a Boost Converter circuit 200, an Output Circuit202 and a Control Circuit 210. The battery 115, boost converter circuit200, output circuit 202 and control circuit 210 are all housed within anhermetically sealed housing 124.

As controlled by the control circuit 210, the output circuit 202 of theIEAD 100 generates a sequence of stimulation pulses that are deliveredto electrodes E1 and E2, through feed-through terminals 206 and 207,respectively, in accordance with a prescribed stimulation regimen. Acoupling capacitor C_(C) is also employed in series with at least one ofthe feed-through terminals 206 or 207 to prevent DC (direct current)current from flowing into the patient's body tissue.

As explained more fully below in connection with the description ofFIGS. 15A and 15B, the prescribed stimulation regimen comprises acontinuous stream of stimulation pulses having a fixed amplitude, e.g.,V_(A) volts, a fixed pulse width, e.g., 0.5 millisecond, and at a fixedfrequency, e.g., 2 Hz, during each stimulation session. The stimulationsession, also as part of the stimulation regimen, is generated at a verylow duty cycle, e.g., for 30 minutes once each week.

In one preferred embodiment, the electrodes E1 and E2 form an integralpart of the housing 124. That is, electrode E2 may comprise acircumferential anode electrode that surrounds a cathode electrode E1.The cathode electrode E1, for the embodiment described here, iselectrically connected to the case 124 (thereby making the feed-throughterminal 206 unnecessary).

In a second preferred embodiment, particularly well-suited forimplantable electrical stimulation devices, the anode electrode E2 iselectrically connected to the case 124 (thereby making the feed-throughterminal 207 unnecessary). The cathode electrode E1 is electricallyconnected to the circumferential electrode that surrounds the anodeelectrode E2. That is, the stimulation pulses delivered to the targettissue location (i.e., to the selected acupoint) through the electrodesE1 and E2 are, relative to a zero volt ground (GND) reference, negativestimulation pulses, as shown in the waveform diagram near the lowerright hand corner of FIG. 8A.

Thus, in the embodiment described in FIG. 8A, it is seen that during astimulation pulse the electrode E2 functions as an anode, or positive(+) electrode, and the electrode E1 functions as a cathode, or negative(−) electrode.

The battery 115 provides all of the operating power needed by the EAdevice 100. The battery voltage V_(BAT) is not the optimum voltageneeded by the circuits of the EA device, including the output circuitry,in order to efficiently generate stimulation pulses of amplitude, e.g.,−V_(A) volts. The amplitude V_(A) of the stimulation pulses is typicallymany times greater than the battery voltage V_(BAT). This means that thebattery voltage must be “boosted”, or increased, in order forstimulation pulses of amplitude V_(A) to be generated. Such “boosting”is done using the boost converter circuit 200. That is, it is thefunction of the Boost Converter circuit 200 to take its input voltage,V_(BAT), and convert it to another voltage, e.g., V_(OUT), which voltageV_(OUT) is needed by the output circuit 202 in order for the IEAD 100 toperform its intended function.

The IEAD 100 shown in FIG. 8A, and packaged as described above inconnection with FIGS. 1-7, advantageously provides a tinyself-contained, coin-sized stimulator that may be implanted in a patientat or near a specified acupoint in order to favorably treat a conditionor disease of a patient. The coin-sized stimulator advantageouslyapplies electrical stimulation pulses at very low levels and low dutycycles in accordance with specified stimulation regimens throughelectrodes that form an integral part of the housing of the stimulator.A tiny battery inside of the coin-sized stimulator provides enoughenergy for the stimulator to carry out its specified stimulation regimenover a period of several years. Thus, the coin-sized stimulator, onceimplanted, provides an unobtrusive, needleless, long-lasting, safe,elegant and effective mechanism for treating certain conditions anddiseases that have long been treated by acupuncture orelectroacupuncture.

A boost converter integrated circuit (IC) typically draws current fromits power source in a manner that is proportional to the differencebetween the actual output voltage V_(OUT) and a set point outputvoltage, or feedback signal. A representative boost converter circuitthat operates in this manner is shown in FIG. 8B. At boost converterstart up, when the actual output voltage is low compared to the setpoint output voltage, the current drawn from the power source can bequite large. Unfortunately, when batteries are used as power sources,they have internal voltage losses (caused by the battery's internalimpedance) that are proportional to the current drawn from them. Thiscan result in under voltage conditions when there is a large currentdemand from the boost converter at start up or at high instantaneousoutput current. Current surges and the associated under voltageconditions can lead to undesired behavior and reduced operating life ofan implanted electro-acupuncture device.

In the boost converter circuit example shown in FIG. 8A, the battery ismodeled as a voltage source with a simple series resistance. Withreference to the circuit shown in FIG. 8A, when the series resistanceRBAT is small (5 Ohms or less), the boost converter input voltageV_(IN), output voltage V_(OUT) and current drawn from the battery,I_(BAT), typically look like the waveform shown in FIG. 9A, where thehorizontal axis is time, and the vertical axis on the left is voltage,and the vertical axis of the right is current.

Referring to the waveform in FIG. 9A, at boost converter startup (10ms), there is 70 mA of current drawn from the battery with only −70 mVof drop in the input voltage V_(IN). Similarly, the instantaneous outputcurrent demand for electro-acupuncture pulses draws up to 40 mA from thebattery with an input voltage drop of ˜40 mV.

Disadvantageously, however, a battery with higher internal impedance(e.g., 160 Ohms), cannot source more than a milliampere or so of currentwithout a significant drop in output voltage. This problem is depictedin the timing waveform diagram shown in FIG. 9B. In FIG. 9B, as in FIG.9A, the horizontal axis is time, the left vertical axis is voltage, andthe right vertical axis is current.

As seen in FIG. 9B, as a result of the higher internal batteryimpedance, the voltage at the battery terminal (V_(IN)) is pulled downfrom 2.9 V to the minimum input voltage of the boost converter (˜1.5 V)during startup and during the instantaneous output current loadassociated with electro-acupuncture stimulus pulses. The resulting dropsin output voltage V_(OUT) are just not acceptable in any type of circuitexcept an uncontrolled oscillator circuit.

Also, it should be noted that although the battery used in the boostconverter circuit is modeled in FIG. 8B as a simple series resistor,battery impedance can arise from the internal design, battery electrodesurface area and different types of electrochemical reactions. All ofthese contributors to battery impedance can cause the voltage of thebattery at the battery terminals to decrease as the current drawn fromthe battery increases.

In a suitably small and thin implantable electroacupuncture device(IEAD) of the type disclosed herein, it is desired to use a higherimpedance battery in order to assure a small and thin device, keep costslow, and/or to have low self-discharge rates. The battery internalimpedance also typically increases as the battery discharges. This canlimit the service life of the device even if a new battery hasacceptably low internal impedance. Thus, it is seen that for the IEAD100 disclosed herein to reliably perform its intended function over along period of time, a circuit design is needed for the boost convertercircuit that can manage the instantaneous current drawn from V_(IN) ofthe battery. Such current management is needed to prevent the battery'sinternal impedance from causing V_(IN) to drop to unacceptably lowlevels as the boost converter circuit pumps up the output voltageV_(OUT) and when there is high instantaneous output current demand, asoccurs when EA stimulation pulses are generated.

To provide this needed current management, the IEAD 100 disclosed hereinemploys electronic circuitry as shown in FIG. 10, or equivalentsthereof. Similar to what is shown in FIG. 8B, the circuitry of FIG. 10includes a battery, a boost converter circuit 200, an output circuit230, and a control circuit 220. The control circuit 220 generates adigital control signal that is used to duty cycle the boost convertercircuit 200 ON and OFF in order to limit the instantaneous current drawnfrom the battery. That is, the digital control signal pulses the boostconverter ON for a short time, but then shuts the boost converter downbefore a significant current can be drawn from the battery. Inconjunction with such pulsing, an input capacitance C_(F) is used toreduce the ripple in the input voltage V_(IN). The capacitor C_(F)supplies the high instantaneous current for the short time that theboost converter is ON and then recharges more slowly from the batteryduring the interval that the boost converter is OFF.

In the circuitry shown in FIG. 10, it is noted that the output voltageV_(OUT) generated by the boost converter circuit 200 is set by thereference voltage V_(REF) applied to the set point or feedback terminalof the boost converter circuit 200. For the configuration shown in FIG.10, V_(REF) is proportional to the output voltage V_(OUT), as determinedby the resistor dividing network of R1 and R2.

The switches S_(P) and S_(R), shown in FIG. 10 as part of the outputcircuit 230, are also controlled by the control circuit 220. Theseswitches are selectively closed and opened to form the EA stimulationpulses applied to the load, R_(LOAD). Before a stimulus pulse occurs,switch S_(R) is closed sufficiently long for the circuit side ofcoupling capacitor C_(C) to be charged to the output voltage, V_(OUT).The tissue side of C_(C) is maintained at 0 volts by the cathodeelectrode E2, which is maintained at ground reference. Then, for most ofthe time between stimulation pulses, both switches S_(R) and S_(P) arekept open, with a voltage approximately equal to the output voltageV_(OUT) appearing across the coupling capacitor C_(C).

At the leading edge of a stimulus pulse, the switch S_(P) is closed,which immediately causes a negative voltage −V_(OUT) to appear acrossthe load, R_(LOAD), causing the voltage at the anode E1 to also drop toapproximately −V_(OUT), thereby creating the leading edge of thestimulus pulse. This voltage starts to decay back to 0 volts ascontrolled by an RC (resistor-capacitance) time constant that is longcompared with the desired pulse width. At the trailing edge of thepulse, before the voltage at the anode E1 has decayed very much, theswitch S_(P) is open and the switch S_(R) is closed. This action causesthe voltage at the anode E1 to immediately (relatively speaking) returnto 0 volts, thereby defining the trailing edge of the pulse. With theswitch S_(R) closed, the charge on the circuit side of the couplingcapacitor C_(C) is allowed to charge back to V_(OUT) within a timeperiod controlled by a time constant set by the values of capacitorC_(C) and resistor R3. When the circuit side of the coupling capacitorC_(C) has been charged back to V_(OUT), then switch S_(R) is opened, andboth switches S_(R) and S_(P) remain open until the next stimulus pulseis to be generated. Then the process repeats each time a stimulus pulseis to be applied across the load.

Thus, it is seen that in one embodiment of the electronic circuitry usedwithin the IEAD 100, as shown in FIG. 10, a boost converter circuit 200is employed which can be shut down with a control signal. The controlsignal is ideally a digital control signal generated by a controlcircuit 220 (which may be realized using a microprocessor or equivalentcircuit). The control signal is applied to the low side (ground side) ofthe boost converter circuit 200 (identified as the “shutdown” terminalin FIG. 10). A capacitor C_(F) supplies instantaneous current for theshort ON time that the control signal enables the boost convertercircuit to operate. And, the capacitor C_(F) is recharged from thebattery during the relatively long OFF time when the control signaldisables the boost converter circuit.

An alternate embodiment of the electronic circuitry that may be usedwithin the IDEA 100 is shown in FIG. 11. This circuit is in mostrespects the same as the circuitry shown in FIG. 10. However, in thisalternate embodiment shown in FIG. 11, the boost converter circuit 200does not have a specific shut down input control. Rather, as seen inFIG. 11, the boost converter circuit is shut down by applying a controlvoltage to the feedback input of the boost converter circuit 200 that ishigher than V_(REF). When this happens, i.e., when the control voltageapplied to the feedback input is greater than V_(REF), the boostconverter will stop switching and draws little or no current from thebattery. The value of V_(REF) is typically a low enough voltage, such asa 1.2 V band-gap voltage, that a low level digital control signal can beused to disable the boost converter circuit. To enable the boostconverter circuit, the control signal can be set to go to a highimpedance, which effectively returns the node at the V_(REF) terminal tothe voltage set by the resistor divider network formed from R1 and R2.Alternatively the control signal can be set to go to a voltage less thanV_(REF).

A low level digital control signal that performs this function ofenabling (turning ON) or disabling (turning OFF) the boost convertercircuit is depicted in FIG. 11 as being generated at the output of acontrol circuit 220. The signal line on which this control signal ispresent connects the output of the control circuit 220 with the V_(REF)node connected to the feedback input of the boost converter circuit.This control signal, as suggested by the waveform shown in FIG. 11,varies from a voltage greater than V_(REF), thereby disabling or turningOFF the boost converter circuit, to a voltage less than V_(REF), therebyenabling or turning the boost converter circuit ON.

A refinement to the alternate embodiment shown in FIG. 11 is to use thecontrol signal to drive the low side of R2 as shown in FIG. 12. That is,as shown in FIG. 12, the boost converter circuit 200 is shut down whenthe control signal is greater than V_(REF) and runs when the controlsignal is less than V_(REF). A digital control signal can be used toperform this function by switching between ground and a voltage greaterthan V_(REF). This has the additional possibility of delta-sigmamodulation control of V_(OUT) if a measurement of the actual V_(OUT) isavailable for feedback, e.g., using a signal line 222, to thecontroller.

One preferred embodiment of the circuitry used in an implantableelectroacupuncture device (IEAD) 100 that employs a digital controlsignal as taught herein is shown in the schematic diagram shown in FIG.13A. In FIG. 13A, there are basically four integrated circuits (ICs)used as the main components. The IC U1 is a boost converter circuit, andperforms the function of the boost converter circuit 200 describedpreviously in connection with FIGS. 8B, 10, 11 and 12.

The IC U2 is a micro-controller IC and is used to perform the functionof the control circuit 220 described previously in connection with FIGS.10, 11 and 12. A preferred IC for this purpose is a MSP430G24521micro-controller chip made by Texas Instruments. This chip includes 8 KBof Flash memory. Having some memory included with the micro-controlleris important because it allows the parameters associated with a selectedstimulation regimen to be defined and stored. One of the advantages ofthe IEAD described herein is that it provides a stimulation regimen thatcan be defined with just 5 parameters, as taught below in connectionwith FIGS. 15A and 15B. This allows the programming features of themicro-controller to be carried out in a simple and straightforwardmanner.

The micro-controller U2 primarily performs the function of generatingthe digital signal that shuts down the boost converter to prevent toomuch instantaneous current from being drawn from the battery V_(BAT).The micro-controller U2 also controls the generation of the stimuluspulses at the desired pulse width and frequency. It further keeps trackof the time periods associated with a stimulation session, i.e., when astimulation session begins and when it ends.

The micro-controller U2 also controls the amplitude of the stimuluspulse. This is done by adjusting the value of a current generated by aProgrammable Current Source U3. In one embodiment, U3 is realized with avoltage controlled current source IC. In such a voltage controlledcurrent source, the programmed current is set by a programmed voltageappearing across a fixed resistor R5, i.e., the voltage appearing at the“OUT” terminal of U3. This programmed voltage, in turn, is set by thevoltage applied to the “SET” terminal of U3. That is, the programmedcurrent source U3 sets the voltage at the “OUT” terminal to be equal tothe voltage applied to the “SET” terminal. The programmed current thatflows through the resistor R5 is then set by Ohms Law to be the voltageat the “set” terminal divided by R5. As the voltage at the “set”terminal changes, the current flowing through resistor R5 at the “OUT”terminal changes, and this current is essentially the same as thecurrent pulled through the closed switch M1, which is essentially thesame current flowing through the load R_(LOAD). Hence, whatever currentflows through resistor R5, as set by the voltage across resistor R5, isessentially the same current that flows through the load R_(LOAD). Thus,as the micro-controller U2 sets the voltage at the “set” terminal of U3,on the signal line labeled “AMPSET”, it controls what current flowsthrough the load R_(LOAD). In no event can the amplitude of the voltagepulse developed across the load R_(LOAD) exceed the voltage V_(OUT)developed by the boost converter less the voltage drops across theswitches and current source.

The switches S_(R) and S_(P) described previously in connection withFIGS. 10, 11 and 12 are realized with transistor switches M1, M2, M3,M4, M5 and M6, each of which is controlled directly or indirectly bycontrol signals generated by the micro-controller circuit U2. For theembodiment shown in FIG. 13A, these switches are controlled by twosignals, one appearing on signal line 234, labeled PULSE, and the otherappearing on signal line 236, labeled RCHG (which is an abbreviation for“recharge”). For the circuit configuration shown in FIG. 13A, the RCHGsignal on signal line 236 is always the inverse of the PULSE signalappearing on signal line 234. This type of control does not allow bothswitch M1 and switch M2 to be open or closed at the same time. Rather,switch M1 is closed when switch M2 is open, and switch M2 is closed,when switch M1 is open. When switch M1 is closed, and switch M2 is open,the stimulus pulse appears across the load, R_(LOAD), with the currentflowing through the load, R_(LOAD), being essentially equal to thecurrent flowing through resistor R5. When the switch M1 is open, andswitch M2 is closed, no stimulus pulse appears across the load, and thecoupling capacitors C5 and C6 are recharged through the closed switch M2and resistor R6 to the voltage V_(OUT) in anticipation of the nextstimulus pulse.

The circuitry shown in FIG. 13A is only exemplary of one type of circuitthat may be used to control the pulse width, amplitude, frequency, andduty cycle of stimulation pulses applied to the load, R_(LOAD). Any typeof circuit, or control, that allows stimulation pulses of a desiredmagnitude (measured in terms of pulse width, frequency and amplitude,where the amplitude may be measured in current or voltage) to be appliedthrough the electrodes to the patient at the specified acupoint at adesired duty cycle (stimulation session duration and frequency) may beused. However, for the circuitry to perform its intended function over along period of time, e.g., years, using only a small energy source,e.g., a small coin-sized battery having a high battery impedance and arelatively low capacity, the circuitry must be properly managed andcontrolled to prevent excessive current draw from the battery.

It is also important that the circuitry used in the IEAD 100, e.g., thecircuitry shown in FIGS. 10, 11, 12, 13A, or equivalents thereof, havesome means for controlling the stimulation current that flows throughthe load, R_(LOAD), which load may be characterized as the patient'stissue impedance at and around the acupoint being stimulated. Thistissue impedance, as shown in FIGS. 11 and 12, may typically vary frombetween about 300 ohms to 2000 ohms. Moreover, it not only varies fromone patient to another, but it varies over time. Hence, there is a needto control the current that flows through this variable load, R_(LOAD).One way of accomplishing this goal is to control the stimulationcurrent, as opposed to the stimulation voltage, so that the same currentwill flow through the tissue load regardless of changes that may occurin the tissue impedance over time. The use of a voltage controlledcurrent source U3, as shown in FIG. 13A, is one way to satisfy thisneed.

Still referring to FIG. 13A, a fourth IC U4 is connected to themicro-controller U2. For the embodiment shown in FIG. 13A, the IC U4 isan electromagnetic field sensor, and it allows the presence of anexternally-generated (non-implanted) electromagnetic field to be sensed.An “electromagnetic” field, for purposes of this application includesmagnetic fields, radio frequency (RF) fields, light fields, and thelike. The electromagnetic sensor may take many forms, such as anywireless sensing element, e.g., a pickup coil or RF detector, a photondetector, a magnetic field detector, and the like. When a magneticsensor is employed as the electromagnetic sensor U4, the magnetic fieldis generated using an External Control Device (ECD) 240 thatcommunicates wirelessly, e.g., through the presence or absence of amagnetic field, with the magnetic sensor U4. (A magnetic field, or othertype of field if a magnetic field is not used, is symbolicallyillustrated in FIG. 13A by the wavy line 242.) In its simplest form, theECD 240 may simply be a magnet, and modulation of the magnetic field isachieved simply by placing or removing the magnet next to or away fromthe IEAD. When other types of sensors (non-magnetic) are employed, theECD 240 generates the appropriate signal or field to be sensed by thesensor that is used.

Use of the ECD 240 provides a way for the patient, or medical personnel,to control the IEAD 100 after it has been implanted (or before it isimplanted) with some simple commands, e.g., turn the IEAD ON, turn theIEAD OFF, increase the amplitude of the stimulation pulses by oneincrement, decrease the amplitude of the stimulation pulses by oneincrement, and the like. A simple coding scheme may be used todifferentiate one command from another. For example, one coding schemeis time-based. That is, a first command is communicated by holding amagnet near the IEAD 100, and hence near the magnetic sensor U4contained within the IEAD 100, for differing lengths of time. If, forexample, a magnet is held over the IEAD for at least 2 seconds, but nomore than 7 seconds, a first command is communicated. If a magnet isheld over the IEAD for at least 11 seconds, but no more than 18 seconds,a second command is communicated, and so forth.

Another coding scheme that could be used is a sequence-based codingscheme. That is, application of 3 magnetic pulses may be used to signalone external command, if the sequence is repeated 3 times. A sequence of2 magnetic pulses, repeated twice, may be used to signal anotherexternal command. A sequence of one magnetic pulse, followed by asequence of two magnetic pulses, followed by a sequence of threemagnetic pulses, may be used to signal yet another external command.

Other simple coding schemes may also be used, such as the letters AA,RR, HO, BT, KS using international Morse code. That is, the Morse codesymbols for the letter “A” are dot dash, where a dot is a short magneticpulse, and a dash is a long magnetic pulse. Thus, to send the letter Ato the IEAD 100 using an external magnet, the user would hold the magnetover the area where the IEAD 100 is implanted for a short period oftime, e.g., one second or less, followed by holding the magnet over theIEAD for a long period of time, e.g., more than one second.

More sophisticated magnetic coding schemes may be used to communicate tothe micro-controller chip U2 the operating parameters of the IEAD 100.For example, using an electromagnet controlled by a computer, the pulsewidth, frequency, and amplitude of the EA stimulation pulses used duringeach stimulation session may be pre-set. Also, the frequency of thestimulation sessions can be pre-set. Additionally, a master reset signalcan be sent to the device in order to re-set these parameters to defaultvalues. These same operating parameters and commands may be re-sent atany time to the IEAD 100 during its useful lifetime should changes inthe parameters be desired or needed.

The current and voltage waveforms associated with the operation of theIEAD circuitry of FIG. 13A are shown in FIG. 13B. In FIG. 13B, thehorizontal axis is time, the left vertical axis is voltage, and theright vertical axis is current. The battery in this example has 160 Ohmsof internal impedance.

Referring to FIGS. 13A and 13B, during startup, the boost converter ONtime is approximately 30 microseconds applied every 7.8 milliseconds.This is sufficient to ramp the output voltage V_(OUT) up to over 10 Vwithin 2 seconds while drawing no more than about 1 mA from the batteryand inducing only 150 mV of input voltage ripple.

The electroacupuncture (EA) simulation pulses resulting from operationof the circuit of FIG. 13A have a width of 0.5 milliseconds and increasein amplitude from approximately 1 mA in the first pulse to approximately15 mA in the last pulse. The instantaneous current drawn from thebattery is less than 2 mA for the EA pulses and the drop in batteryvoltage is less than approximately 300 mV. The boost converter isenabled (turned ON) only during the instantaneous output current surgesassociated with the 0.5 milliseconds wide EA pulses.

Another preferred embodiment of the circuitry used in an implantableelectroacupuncture device (IEAD) 100 that employs a digital controlsignal as taught herein is shown in the schematic diagram of FIG. 14.The circuit shown in FIG. 14 is, in most respects, very similar to thecircuit described previously in connection with FIG. 13A. What is new inFIG. 14 is the inclusion of an external Schottky diode D4 at the outputterminal LX of the boost convertor U1 and the inclusion of a fifthintegrated circuit (IC) U5 that essentially performs the same functionas the switches M1-M6 shown in FIG. 13A.

The Schottky diode D5 helps isolate the output voltage V_(OUT) generatedby the boost converter circuit U1. This is important in applicationswhere the boost converter circuit U1 is selected and operated to providean output voltage V_(OUT) that is four or five times as great as thebattery voltage, V_(BAT). For example, in the embodiment for which thecircuit of FIG. 14 is designed, the output voltage V_(OUT) is designedto be nominally 15 volts using a battery that has a nominal batteryvoltage of only 3 volts. (In contrast, the embodiment shown in FIG. 13Ais designed to provide an output voltage that is nominally 10-12 volts,using a battery having a nominal output voltage of 3 volts.)

The inclusion of the fifth IC U5 in the circuit shown in FIG. 14 is, asindicated, used to perform the function of a switch. The other ICs shownin FIG. 14, U1 (boost converter), U2 (micro-controller), U3 (voltagecontrolled programmable current source) and U4 (electromagnetic sensor)are basically the same as the IC's U1, U2, U3 and U4 describedpreviously in connection with FIG. 13A.

The IC U5 shown in FIG. 14 functions as a single pole/double throw(SPDT) switch. Numerous commercially-available ICs may be used for thisfunction. For example, an ADG1419 IC, available from Analog DevicesIncorporated (ADI) may be used. In such IC U5, the terminal “D”functions as the common terminal of the switch, and the terminals “SA”and “SB” function as the selected output terminal of the switch. Theterminals “IN” and “EN” are control terminals to control the position ofthe switch. Thus, when there is a signal present on the PULSE line,which is connected to the “IN” terminal of U5, the SPDT switch U5connects the “D” terminal to the “SB” terminal, and the SPDT switch U5effectively connects the cathode electrode E1 to the programmablecurrent source U3. This connection thus causes the programmed current,set by the control voltage AMPSET applied to the SET terminal of theprogrammable current source U3, to flow through resistor R5, which inturn causes essentially the same current to flow through the load,R_(LOAD), present between the electrodes E1 and E2. When a signal is notpresent on the PULSE line, the SPDT switch U5 effectively connects thecathode electrode E1 to the resistor R6, which allows the couplingcapacitors C12 and C13 to recharge back to the voltage V_(OUT) providedby the boost converter circuit U2.

From the above description, it is seen that an implantable IEAD 100 isprovided that uses a digital control signal to duty-cycle limit theinstantaneous current drawn from the battery by a boost converter. Threedifferent exemplary configurations (FIGS. 10, 11 and 12) are taught forachieving this desired result, and two exemplary circuit designs thatmay be used to realize this result have been disclosed (FIGS. 13A and14). One configuration (FIG. 12) teaches the additional capability todelta-sigma modulate the boost converter output voltage.

Delta-sigma modulation is well described in the art. Basically, it is amethod for encoding analog signals into digital signals orhigher-resolution digital signals into lower-resolution digital signals.The conversion is done using error feedback, where the differencebetween the two signals is measured and used to improve the conversion.The low-resolution signal typically changes more quickly than thehigh-resolution signal and it can be filtered to recover the highresolution signal with little or no loss of fidelity. Delta-sigmamodulation has found increasing use in modern electronic components suchas converters, frequency synthesizers, switched-mode power supplies andmotor controllers. See, e.g., Wikipedia, Delta-sigma modulation.

II. D. Use and Operation

With the implantable electroacupuncture device (IDEA) 100 in hand, theIDEA 100 may be used most effectively to treat cardiovascular disease byfirst pre-setting stimulation parameters that the device will use duringa stimulation session. FIG. 15A shows a timing waveform diagramillustrating the EA stimulation parameters used by the IEAD to generateEA stimulation pulses. As seen in FIG. 15A, there are basically fourparameters associated with a stimulation session. The time T1 definesthe duration (or pulse width) of a stimulus pulse. The time T2 definesthe time between the start of one stimulus pulse and the start of thenext stimulus pulse. The time T2 thus defines the period associated withthe frequency of the stimulus pulses. The frequency of the stimulationpulses is equal to 1/T2. The ratio of T1/T2 is typically quite low,e.g., less than 0.01. The duration of a stimulation session is definedby the time period T3. The amplitude of the stimulus pulses is definedby the amplitude A1. This amplitude may be expressed in either voltageor current.

Turning next to FIG. 15B, a timing waveform diagram is shown thatillustrates the manner in which the stimulation sessions areadministered in accordance with a preferred stimulation regimen. FIG.15B shows several stimulation sessions of duration T3, and how often thestimulation sessions occur. The stimulation regimen thus includes a timeperiod T4 which sets the time period from the start of one stimulationsession to the start of the next stimulation session. T4 thus is theperiod of the stimulation session frequency, and the stimulation sessionfrequency is equal to 1/T4.

One preferred set of parameters to use to define a stimulation regimenare

-   -   T1=0.5 milliseconds    -   T2=500 milliseconds    -   T3=30 minutes    -   T4=7 days (10,080 minutes)    -   A1=6 volts (across 1 kOhm)

It is to be emphasized that the values shown above for the stimulationregimen are representative of only one preferred stimulation regimenthat could be used. Other stimulation regimens that could be used, andthe ranges of values that could be used for each of these parameters,are as defined in the claims.

It is also emphasized that the ranges of values presented in the claimsfor the parameters used with the invention have been selected after manymonths of careful research and study, and are not arbitrary. Forexample, the ratio of T3/T4, which sets the duty cycle, has beencarefully selected to be very low, e.g., no more than 0.05. Maintaininga low duty cycle of this magnitude represents a significant change overwhat others have attempted in the implantable stimulator art. Not onlydoes a very low duty cycle allow the battery life to be extended, whichin turn allows the IEAD housing to be very small, which makes the IEADideally suited for being used without leads, thereby making itrelatively easy to implant the device at the desired acupuncture site,but it also limits the frequency and duration of stimulation sessions.Limiting the frequency and duration of the stimulation sessions is a keyaspect of applicants' invention because it recognizes that sometreatments, such as treating cardiovascular disease, are best doneslowly and methodically, over time, rather than quickly and harshlyusing large doses of stimulation (or other treatments) aimed at forcinga rapid change in the patient's condition. Moreover, applying treatmentsslowly and methodically is more in keeping with traditional acupuncturemethods (which, as indicated previously, are based on over 2500 years ofexperience). In addition, this slow and methodical conditioning isconsistent with the time scale for remodeling of the central nervoussystem needed to produce the sustained therapeutic effect. Thus,applicants have based their treatment regimens on theslow-and-methodical approach, as opposed to the immediate-and-forcedapproach adopted by many, if not most, prior art implantable electricalstimulators.

Once the stimulation regimen has been defined and the parametersassociated with it have been pre-set into the memory of themicro-controller circuit 220, the IEAD 100 needs to be implanted.Implantation is a simple procedure, and is described above in connectionwith the description of FIGS. 1A and 1B.

For treating heart failure, coronary artery disease, myocardial ischemiaor angina, the specified acupoint at which the EA stimulation pulsesshould be applied in accordance with a selected stimulation regimen isat least one of the following acupoints: PC6, ST36, BL14 (also referredto as UB14), EX-HN1 (located approximately one centimeter from GV20),HT7, HT5, LI11, LU2 and LU7.

After implantation, the IEAD must be turned ON, and otherwisecontrolled, so that the desired stimulation regimen may be carried out.In one preferred embodiment, control of the IEAD after implantation, aswell as anytime after the housing of the IEAD has been hermeticallysealed, is performed as shown in the state diagram of FIG. 16. Eachcircle shown in FIG. 16 represents a “state” that the micro-controllerU2 (in FIG. 13A or 14) may operate in under the conditions specified. Asseen in FIG. 16, the controller U2 only operates in one of six states:(1) a “Set Amplitude” state, (2) a “Shelf Mode” state, (3) a “TriggeredSession” state, (4) a “Sleep” state, (5) an “OFF” state, and an (6)“Automatic Session” state. The “Automatic Session” state is the statethat automatically carries out the stimulation regimen using thepre-programmed parameters that define the stimulation regimen.

Shelf Mode is a low power state in which the IEAD is placed prior toshipment. After implant, commands are made through magnet application.Magnet application means an external magnet, typically a small hand-heldcylindrical magnet, is placed over the location where the IEAD has beenimplanted. With a magnet in that location, the magnetic sensor U4 sensesthe presence of the magnet and notifies the controller U2 of themagnet's presence.

From the “Shelf Mode” state, a magnet application for 10 seconds (M.10s) puts the IEAD in the “Set Amplitude” state. While in the “SetAmplitude” state, the stimulation starts running by generating pulses atzero amplitude, incrementing every five seconds until the patientindicates that a comfortable level has been reached. At that time, themagnet is removed to set the amplitude.

If the magnet is removed and the amplitude is non-zero ( M̂A), the devicecontinues into the “Triggered Session” so the patient receives theinitial therapy. If the magnet is removed during “Set Amplitude” whilethe amplitude is zero ( M̂Ā), the device returns to the Shelf Mode.

The Triggered Session ends and stimulation stops after the session time(T_(S)) has elapsed and the device enters the “Sleep” state. If a magnetis applied during a Triggered Session (M), the session aborts to the“OFF” state. If the magnet remains held on for 10 seconds (M.10 s) whilein the “OFF” state, the “Set Amplitude” state is entered with thestimulation level starting from zero amplitude as described.

If the magnet is removed ( M) within 10 seconds while in the OFF state,the device enters the Sleep state. From the Sleep state, the deviceautomatically enters the Automatic Session state when the sessioninterval time has expired (T_(I)). The Automatic Session deliversstimulation for the session time (T_(S)) and the device returns to theSleep state. In this embodiment, the magnet has no effect once theAutomatic Session starts so that the full therapy session is delivered.

While in the Sleep state, if a magnet has not been applied in the last30 seconds (D) and a magnet is applied for a window between 20-25seconds and then removed (M.20:25 s), a Triggered Session is started. Ifthe magnet window is missed (i.e. magnet removed too soon or too late),the 30 second de-bounce period (D) is started. When de-bounce is active,no magnet must be detected for 30 seconds before a Triggered Session canbe initiated.

The session interval timer runs while the device is in Sleep state. Thesession interval timer is initialized when the device is woken up fromShelf Mode and is reset after each session is completely delivered. Thusabort of a triggered session by magnet application will not reset thetimer, the Triggered Session must be completely delivered.

The circuitry that sets the various states shown in FIG. 16 as afunction of externally-generated magnetic control commands, or otherexternally-generated command signals, is the micro-controller U2 (FIG.14), the processor U2 (FIG. 13A), or the control circuit 220 (FIGS. 10,11 and 12). Such processor-type circuits are programmable circuits thatoperate as directed by a program. The program is often referred to as“code”, or a sequence of steps that the processor circuit follows. The“code” can take many forms, and be written in many different languagesand formats, known to those of skill in the art. Representative “code”for the micro-controller U2 (FIG. 14) for controlling the states of theIEAD as shown in FIG. 16 is found in Appendix C, attached hereto, andincorporated by reference herein.

Relationship with Applicant's Other Inventions

Readers of this patent application who have also read Applicant'scopending patent application(s) and issued patent(s) relating to thetreatment of hypertension using a small, implantable EA device of thetype described herein, will recognize that the treatment described therefor hypertension treatment, including one of the acupoints, PC6, wherethe stimulation pulses are applied, is essentially the same as thatdescribed herein for the treatment of the four conditions ofcardiovascular disease (heart failure, CAD, myocardial ischemia andangina) that are the focus of this patent application. Why is this? Arethe inventions the same invention? The answer is that while theapparatus (the small implantable EA device) is essentially the same, andthe stimulation regimen and point of application are essentially thesame (or at least potentially may be the same depending upon theparticular acupoint selected and the particular stimulation regimenparameters selected), the inventions target different conditions, andhence are different. Just like a wrench, for example, is a tool that maybe used, sometimes alone but most often in combination with other tools,for a wide variety of applications, the EA device described herein, andits manner of use, may be used, sometimes alone but most often incombination with other tools, for a wide variety of beneficialapplications, one of which is treating various conditions associatedwith cardiovascular disease, and another of which is treatinghypertension.

The close relationship between the two inventions (hypertensiontreatment and cardiovascular disease treatment) makes sense. In additionto heart failure, the sympathetic nervous system (SNS) is increased inthe other conditions Applicant treats with this invention—in coronaryartery disease, angina, and myocardial ischemia. Raised sympatheticnervous activity is the common denominator. And while a patient with oneof these aforementioned conditions may or may not be hypertensive, themechanism of action brought about by the device and methods disclosed inApplicant's hypertension treatment patent application involves thereduction of sympathetic activity. That is, the effect on bloodpressure, Applicant submits, from the use of their EA device at acupointPC6 (Neiguan), is secondary and results from the inhibiting effect onthe SNS.

For example, in experimental models, it has been demonstrated that lowfrequency electroacupuncture (EA) stimulation at acupoint PC6 (Neiguan)effectively stimulates somatic afferents to provide input to regionssuch as the rVLM that regulates sympathetic outflow. See, Zhou W Y,Tjen-A-Looi S C, Longhurst J C, “Brain stem mechanisms underlyingacupuncture modality-related modulation of cardiovascular responses inrats,” J Appl Physiol 2005, 99:851-860; Zhou W, Fu L W, Tjen-A-Looi S C,et al., “Afferent mechanisms underlying stimulation of modality-relatedmodulation of acupuncture-related cardiovascular responses,” J ApplPhysiol 2005, 98:872-880. Furthermore, in experiments measuring theeffect of stimulating acupoint PC6 (Neiguan) on blood pressure, theextent of blood pressure depression is dependent on the extent ofconvergent input to premotor sympathetic neurons in the rVLM.Tjen-A-Looi S C, Li P, Longhurst J C. “Medullary substrate anddifferential cardiovascular responses during stimulation of specificacupoints,” Am J Physiol Regul Integr Comp Physiol 2004, 287:R852-R862.Thus, the effect on blood pressure seems to follow the effect onsympathetic activity.

Since Applicant believes the stimulation regimen and target at PC6(Neiguan) disclosed in its hypertension treatment patent applicationrepresents at least one optimal system for reducing sympatheticactivity, it has chosen to apply the same system to the conditionsdisclosed herein for which raised sympathetic activation is problematic.In fact, while much of the acupuncture studies performed at acupoint PC6(Neiguan) were done to treat hypertension, the mechanism by whichApplicant believes hypertension is improved—the reduction of sympatheticactivity—may be more central to the treatment of heart failure. That is,hypertension may not always be driven sympathetically, whereas thehallmark of heart failure is heightened sympathetic drive. Thus, it isimportant that Applicant targets the SNS in the treatment of heartfailure, in particular, by the application of its EA device at acupointPC6 (Neiguan).

In the preceding description, various exemplary embodiments have beendescribed with reference to the accompanying drawings. It will, however,be evident that various modifications and changes may be made thereto,and additional embodiments may be implemented, without departing fromthe scope of the invention as set forth in the claims that follow. Forexample, certain features of one embodiment described herein may becombined with or substituted for features of another embodimentdescribed herein. The description and drawings are accordingly to beregarded in an illustrative rather than a restrictive sense and are notintended to be exhaustive or to limit the invention to any precise formdisclosed. Many modifications and variations are possible in light ofthe above teaching. Thus, while the invention(s) herein disclosed hasbeen described by means of specific embodiments and applicationsthereof, numerous modifications and variations could be made thereto bythose skilled in the art without departing from the scope of theinvention(s) set forth in the claims.

What is claimed is:
 1. A method of treating a cardiovascular disease ina patient, comprising: generating, by an electroacupuncture deviceimplanted beneath a skin surface of the patient at an acupointcorresponding to a median nerve of the patient, stimulation sessions ata duty cycle that is less than 0.05, wherein each stimulation sessionincluded in the plurality of stimulation sessions comprises a series ofstimulation pulses, the duty cycle is a ratio of T3 to T4, eachstimulation session included in the stimulation sessions has a durationof T3 minutes and occurs at a rate of once every T4 minutes, and theelectroacupuncture device comprises a central electrode of a firstpolarity centrally located on a first surface of a housing of theelectroacupuncture device and an annular electrode of a second polarityand that is spaced apart from the central electrode; and applying, bythe electroacupuncture device, the stimulation sessions to the mediannerve by way of the central electrode and the annular electrode inaccordance with the duty cycle.
 2. The method of claim 1, wherein thestimulation sessions are configured to reduce sympathetic activitywithin the patient.
 3. The method of claim 1, wherein the cardiovasculardisease comprises at least one of heart failure, coronary arterydisease, myocardial ischemia, and angina.
 4. The method of claim 1,wherein the acupoint comprises PC6.
 5. The method of claim 1, wherein T3is at least 10 minutes and less than 60 minutes, and wherein T4 is atleast 1440 minutes.
 6. The method of claim 1, further comprising:receiving, by the electroacupuncture device from a device external tothe electroacupuncture device, a control command that sets the times T3and T4 to appropriate values configured to treat the cardiovasculardisease; wherein the generating of the stimulation sessions is performedin accordance with the control command.
 7. The method of claim 6,wherein the receiving of the control command comprises detecting, with amagnetic field sensor included in the electroacupuncture device, amagnetic field generated by the device external to theelectroacupuncture device.
 8. The method of claim 1, wherein the housingis coin-sized and coin-shaped.
 9. The method of claim 1, wherein theannular electrode is located on the first surface of the housing. 10.The method of claim 1, wherein the annular electrode comprises a ringelectrode located around a circumferential edge of the housing.
 11. Themethod of claim 1, wherein the applying of the stimulation sessions tothe median nerve further comprises applying the stimulation sessions byway an electrode included on a lead connected to the electroacupuncturedevice.
 12. The method of claim 1, further comprising poweringelectronic circuits within the electroacupuncture device with a batteryhaving an internal impedance of at least 5 ohms.
 13. A method oftreating heart failure in a patient, comprising: generating, by anelectroacupuncture device implanted beneath a skin surface of thepatient at an acupoint corresponding to a median nerve of the patient,stimulation sessions at a duty cycle that is less than 0.05, whereineach stimulation session included in the plurality of stimulationsessions comprises a series of stimulation pulses, the duty cycle is aratio of T3 to T4, each stimulation session included in the stimulationsessions has a duration of T3 minutes and occurs at a rate of once everyT4 minutes, and the electroacupuncture device comprises a centralelectrode of a first polarity centrally located on a first surface of ahousing of the electroacupuncture device and an annular electrode of asecond polarity and that is spaced apart from the central electrode; andreducing, by the electroacupuncture device, sympathetic activity withinthe patient by applying the stimulation sessions to the median nerve byway of the central electrode and the annular electrode in accordancewith the duty cycle.
 14. The method of claim 13, wherein the acupoint isPC6.
 15. An electroacupuncture device for treating a cardiovasculardisease in a patient, comprising: a housing configured to be implantedbeneath a skin surface of the patient at an acupoint corresponding to amedian nerve of the patient; a central electrode of a first polarity andcentrally located on a first surface of the housing; an annularelectrode of a second polarity and that surrounds the central electrodeon the first surface of the housing, the annular electrode being spacedapart from the central electrode; and pulse generation circuitry locatedwithin the housing and electrically coupled to the annular and centralelectrodes, wherein the pulse generation circuitry generates stimulationsessions at a duty cycle that is less than 0.05, and applies thestimulation sessions to the median nerve by way of the central electrodeand the annular electrode in accordance with the duty cycle, whereineach stimulation session included in the plurality of stimulationsessions comprises a series of stimulation pulses, the duty cycle is aratio of T3 to T4, and each stimulation session included in thestimulation sessions has a duration of T3 minutes and occurs at a rateof once every T4 minutes.
 16. The electroacupuncture device of claim 15,wherein the stimulation sessions are configured to reduce sympatheticactivity within the patient.
 17. The electroacupuncture device of claim15, wherein the cardiovascular disease comprises at least one of heartfailure, coronary artery disease, myocardial ischemia, and angina. 18.The electroacupuncture device of claim 15, wherein the acupointcomprises PC6.
 19. The electroacupuncture device of claim 15, furthercomprising a magnetic field sensor that receives, from a device externalto the electroacupuncture device, a control command that sets the timesT3 and T4 to appropriate values configured to treat the cardiovasculardisease.
 20. The electroacupuncture device of claim 15, furthercomprising a battery that powers the pulse generation circuitry, thebattery having an internal impedance of at least 5 ohms.